Compositions and methods for predicting response and resistance to ctla4 blockade in melanoma using a gene expression signature

ABSTRACT

The present invention relates to compositions and methods for predicting response and resistance to CTA4 blockade in melanoma.

RELATED APPLICATIONS

This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 62/407,591, filed Oct. 13, 2016, and to U.S. Provisional Application No. 62/565,411, filed Sep. 29, 2017, each of which is incorporated herein by reference in its entirety.

GOVERNMENT LICENSE RIGHTS

This invention was made with government support under grant number 1R01CA182461-01 awarded by the National Cancer Institute, under grant number 1R01CA184922-02 awarded by the National Cancer Institute, under grant number R50RCA211482A awarded by the National Cancer Institute, and under grant number 1R01CA155010-05 awarded by the National Cancer Institute. The government has certain rights in the invention.

BACKGROUND OF THE INVENTION

Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) blockade can induce durable clinical remissions in a minority of patients with metastatic melanoma. However, prior to the invention described herein, molecular signatures precisely predicting response and resistance to CTLA4 blockade were unknown. As such, there is a pressing need to identify more effective methods for predicting response or resistance to CTLA4 blockade.

SUMMARY OF THE INVENTION

The invention is based, at least in part, upon the identification of a gene expression signature that discriminates clinical outcomes of CTLA4 blockade. Specifically, described herein is a specific cluster of cancer-testis antigens and microRNA-211 that are predictive of resistance and response, respectively, to ipilimumab in melanoma. In some aspects, the invention relates to methods, arrays, and kits for diagnosing, monitoring, and treating melanoma.

As described in detail below, in one aspect, the invention is a gene expression signature that predicts clinical response and resistance to CTLA4 blockade, e.g., ipilimumab, in patients with metastatic melanoma.

In one aspect, increased expression of at least one of the following genes significantly correlates with resistance to ipilimumab: MAGEA2, CSAG4, MAGEA2B, AC093787 (RP11-215P9), MAGEA12, CSAG1, GABRA3, CSAG3, makorin ring finger protein 9 (MKRN9P), keratin 8 pseudogene 8 (KRT8P8), MAGEA6, EYA1, CSAG2, RP11-379D21.3, MAGE family member C1 (MAGEC1), RP1-273G13.1, MAGEA3, miR-218-1, pregnancy specific beta-1-glycoprotein 11 (PSG11), X-inactive specific transcript (XIST), RP11-360D2.1, pregnancy specific beta-1-glycoprotein 10 pseudogene (PSG10P), miR-1262, tachykinin 3 (TAC3), PSG8, heat shock protein family B (small) member 3 (HSPB3), gap junction protein beta-6 (GJB6), GABRQ, MAGEA1, MAGEA11, MAGEA9B, and PSG6.

A cluster of CT antigen genes on the Xq28 cytoband (i.e., MAGEA2, CSAG4, MAGEA2B, MAGEA12, CSAG1, CSAG3, MAGEA6, CSAG2, MAGEA3) correlate with resistance to ipilimumab. Additionally, miR-211 and transient receptor potential cation channel subfamily M member 1 (TRPM1) (which subsumes miR-211) correlate with response to ipilimumab.

Also provided is a gene expression signature that predicts clinical response and resistance to a combination of an agonist of an HMGB1 pathway, HMGB1 receptor (henceforth “HMGB1 agonist”)(e.g., toll-like receptor (TLR) agonists); or agonist of autophagy (e.g., metformin, temozolomide, trifluoperazine, divalproex sodium, vorinostat, rapamycin, everolimus, MG-132, doxorubicin, ABT-737, BCL2 inhibitors/antagonists, gemcitabine, torin 1, resveratrol, etc); or an agonist of miR-211, miR-185 and/or miR-513A2; or Xq28-CGA antagonist and CTLA4 blockade, e.g., ipilimumab or tremelimumab, in patients with melanoma, e.g., metastatic melanoma. Specifically, increased expression of at least one of the following genes significantly correlates with benefit to treatment with a TLR agonist (or autophagy agonist or Xq28-CGA antagonist) and ipilimumab: MAGEA2, MAGE2AB, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, and CSAG3. For example, the Xq28-CGA inhibitor comprises an antibody, an aptamer, or a small molecule. Additionally, decreased expression of at least one of these genes significantly correlates with benefit to treatment with an agonist of miR-211, miR-185 and/or miR-513A2. For example, the miR agonist comprises a miR mimetic (natural or synthetic) or an aptamer.

Accordingly, provided is a method of determining whether inhibition of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in a subject, e.g., a human subject, with melanoma will result in clinical benefit (e.g., inhibition of melanoma cancer cells) in the subject, comprising: obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether CTLA4 blockade will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample.

Also provided is a method of treating cancer comprising administering an effective amount of a CTLA4 inhibitor and an effective amount of an HMGB1 agonist or autophagy agonist or Xq28-CGA antagonist. For example, the CTLA4 inhibitor comprises ipilumamab. In another example, the HMGB1 agonist comprises high mobility group box 1 (HMGB1), TLR agonists like unmethylated CpG DNA (e.g., CpG-oligodeoxynucleotides or CpG-ODN), Hiltonol (poly-ICLC), Bacillus Calmette-Guérin (BCG), monophosphoryl lipid A (MPL), imiquimod, etc. In other example, the agonist of autophagy comprises inducers of autophagy, e.g., metformin, temozolomide, trifluoperazine, divalproex sodium, vorinostat, mTOR inhibitors (e.g., rapamycin, everolimus), MG-132, doxorubicin, ABT-737, BCL2 inhibitors/antagonists, gemcitabine, torin 1, resveratrol, etc. In other example, the agonist of miR-211, miR-185 and/or miR-513A2 comprises a miR mimetic (synthetic or natural) or an aptamer.

Also provided are methods of determining whether administration of a CTLA4 inhibitor and an HMGB1 agonist to a subject with melanoma will result in clinical benefit in the subject comprising obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether administration of a CTLA4 inhibitor and an HMGB1 agonist will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample.

For example, the test sample is obtained from the melanoma, wherein the melanoma-associated gene comprises a cancer germline antigen (CGA) gene; and determining that administration of the CTLA4 inhibitor and the HMGB1 agonist in a subject with melanoma will result in clinical benefit in the subject if the expression level of the CGA gene in the test sample is higher than the level of the CGA gene in the reference sample.

In one aspect, the CGA gene comprises MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, or CSAG3.

Alternatively, the expression level of the melanoma-associated gene in the test sample is compared with a threshold expression level of the melanoma-associated gene (e.g., a “cut-off level”). The method involves determining whether CTLA4 blockade will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the threshold expression level of the melanoma-associated gene.

In another case, the expression level of the melanoma-associated gene in the test sample is compared with an expression level of a housekeeping gene within the test sample. The method involves determining whether CTLA4 blockade will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the expression level of the housekeeping gene. For example, clinical benefit in the subject comprises complete or partial response or stable disease with overall survival of greater than one year as defined by response evaluation criteria in solid tumors (RECIST). In some cases, clinical benefit is associated with an inhibition of melanoma cells. By contrast, the absence of clinical benefit (i.e., no clinical benefit) in the subject comprises progressive disease or stable disease with overall survival of less than one year as defined by RECIST. Alternatively or in addition to using RECIST, clinical benefit in the subject is evaluated using immune-related response criteria (irRC). For example, clinical benefit comprises long-term survival in spite of disease progression or response defined by irRC criteria

The expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample, the threshold expression level, or the expression level of a housekeeping gene. For example, the expression level of the melanoma-associated gene in the test sample is upregulated (i.e., increased) by at least 2 fold, at least 3 fold, at least 4 fold, at least 5 fold, at least 6 fold, at least 7 fold, at least 8 fold, at least 9 fold, at least 10 fold, at least 15 fold, at least 20 fold, at least 25 fold, at least 30 fold, at least 35 fold, at least 40 fold, at least 45 fold, at least 50 fold, at least 60 fold, at least 70 fold, at least 80 fold, at least 90 fold, at least 100 fold, at least 125 fold, at least 150 fold, at least 175 fold, at least 200 fold, at least 250 fold, at least 300 fold, at least 350 fold, at least 400 fold, at least 500 fold, at least 600 fold, at least 700 fold or at least 800 fold as compared to the level of the melanoma-associated gene in the reference sample, the threshold expression level, or the expression level of a housekeeping gene.

Alternatively, the expression level of the melanoma-associated gene in the test sample is downregulated (i.e., decreased) by at least 2 fold, at least 3 fold, at least 4 fold, at least 5 fold, at least 6 fold, at least 7 fold, at least 8 fold, at least 9 fold, at least 10 fold, at least 15 fold, at least 20 fold, at least 25 fold, at least 30 fold, at least 35 fold, at least 40 fold, at least 45 fold, at least 50 fold, at least 60 fold, at least 70 fold, at least 80 fold, at least 90 fold, at least 100 fold, at least 125 fold, at least 150 fold, at least 175 fold, at least 200 fold, at least 250 fold, at least 300 fold, at least 350 fold, at least 400 fold, at least 500 fold, at least 600 fold, at least 700 fold or at least 800 fold as compared to the level of the melanoma-associated gene in the reference sample, the threshold expression level, or the expression level of a housekeeping gene.

In one aspect, the test sample is obtained from the melanoma tissue, from the tumor microenvironment, or from tumor-infiltrating immune cells. For example, the test sample is obtained from the melanoma and the melanoma-associated gene comprises a gene on chromosome Xq28. For example, the melanoma-associated gene comprises a cancer germline antigen (CGA) gene (i.e., a cancer-testis (CT) antigen gene); and the method involves determining that inhibition of CTLA4 in a subject with melanoma will not result in clinical benefit in the subject if the expression level of the CGA gene in the test sample is higher than the level of the CGA gene in the reference sample. Exemplary CGA genes include melanoma-associated antigen 2 (MAGEA2), MAGEA3, MAGEA6, MAGEA12, chondrosarcoma associated gene 1 (CSAG1), CSAG2, CSAG3, and CSAG4.

Optionally, the melanoma-associated gene is hypomethylated, e.g., there is a decrease in the epigenetic methylation of cytosine residues in CpG dinucleotides deoxyribonucleic acid (DNA) in the promoter and/or a change in epigenetic methylation of cytosine residues in CpG dinucleotides in the gene body. For example, a CGA gene is hypomethylated in the promoter. For example, local hypomethylation of the Xq28 MAGE genes described herein, e.g., MAGEA2, MAGEA3, MAGEA6, or MAGEA12, is identified. Alternatively, or in addition, global hypomethylation of the genes in the test sample is identified. As described herein, hypomethylation of genes is an indication that inhibition of CTLA4 in a subject with melanoma will not result in clinical benefit in the subject.

Optionally, the melanoma-associated gene is hypermethylated, e.g., there is an increase in the epigenetic methylation of cytosine residues in CpG dinucleotides deoxyribonucleic acid (DNA) in the promoter and/or a change in epigenetic methylation of cytosine residues in CpG dinucleotides in the gene body. For example, a CGA gene is hypermethylated in the promoter. For example, local hypermethylation of the Xq28 MAGE genes described herein is identified. Alternatively, or in addition, global hypermethylation of the genes in the test sample is identified. As described herein, hypermethylation of genes is an indication that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject.

Alternatively, the test sample is obtained from the melanoma and the melanoma-associated gene comprises a pregnancy-specific glycoprotein (PSG) gene, a γ-aminobutyric acid (GABA) A receptor gene, an epithelial-to-mesenchymal transition gene, an embryonic development/differentiation gene, an angiogenesis gene, or an extracellular matrix (ECM) gene; and the method involves determining that inhibition of CTLA4 in a subject with melanoma will not result in clinical benefit in the subject if the expression level of the PSG gene, GABA A receptor gene, epithelial-to-mesenchymal transition gene, embryonic development/differentiation gene, angiogenesis gene, or extracellular matrix gene in the test sample is higher than the level of the respective gene in the reference sample.

Exemplary PSG genes include PSG1, PSG2, PSG4, PSG5, PSG6, PSG7, PSG8, PSG9, and PSG11. In some cases, the PSG gene is hypomethylated. Suitable GABA A receptor genes include gamma-aminobutyric acid type A receptor alpha 3 subunit (GABRA3), gamma-aminobutyric acid type A receptor beta 1 subunit (GABRB1), GABRB2, gamma-aminobutyric acid type A receptor gamma 2 subunit (GABRG2), gamma-aminobutyric acid type A receptor theta subunit (GABRQ), gamma-aminobutyric acid type A receptor rho 1 subunit (GABRR1). In one aspect, the epithelial-to-mesenchymal transition gene comprises claudin 1 (CLDN1), CLDN2, eyes absent homolog 1 (EYA1), snail family zinc finger 1 (SNAI1), transforming growth factor beta 2 (TGFB2), or wingless-type MMTV integration site family member 3 (WNT3). Exemplary embryonic development/differentiation genes include homeobox D13 (HOXD13), HOXD11, HOXA2, HOXA5, and HOXD10. In some cases, the angiogenesis gene comprises angiopoietin 1 (ANGPT1), angiopoietin-2 (ANG2), or platelet derived growth factor subunit A (PDGFA). Suitable ECM genes include protocadherin beta 2 (PCDHB2), PCDHB3, PCDHB6, PCDHB10, protocadherin gamma subfamily A3, (PCDHGA3), PCDHGB1, PCDHGB2, elastin microfibril interfacer 1 (EMILIN1), and tenascin N (TNN).

In other cases, the test sample is obtained from the melanoma, and the melanoma-associated gene comprises micro ribonucleic acid-211 (miR-211), miR-513A2, or miR-185. It is determined that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of miR-211, miR-513A2, or miR-185 in the test sample is higher than the level of miR-211, miR-513A2, or miR-185, respectively, in the reference sample.

In other cases, the test sample is obtained from the melanoma, and the melanoma-associated gene comprises melastatin-1 (TRPM1). It is determined that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of TRPM1 in the test sample is higher than the level of TRPM1 in the reference sample.

In one aspect, the test sample is obtained from the melanoma and the melanoma-associated gene comprises miR-211, cluster of differentiation 5 molecule like (CD5L), interleukin 12 receptor subunit beta 2 (IL12RB2), fas apoptotic inhibitory molecule 3 (FAIM3), and/or pre T-Cell antigen receptor alpha (PTCRA). It is determined that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of miR-211, CD5L, IL12RB2, FAIM3, and PTCRA in the test sample is higher than the level of the corresponding gene in the reference sample.

In another aspect, the test sample is obtained from the melanoma, and the melanoma-associated gene comprises miR-211, MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, CSAG3, or CSAG4. It is determined that inhibition of CTLA4 in a subject with melanoma will not result in clinical benefit in the subject if the expression level of miR-211 in the test sample is lower than the level of miR-211 in the reference sample and if the expression level of MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, CSAG3, and CSAG4 in the test sample is higher than the level of the corresponding gene in the reference sample.

Alternatively, the test sample is obtained from a melanoma or the infiltrating immune cells, wherein the melanoma-associated gene comprises a T cell infiltration-associated gene, a receptor signaling gene, an activation gene, a cytotoxicity gene, a humoral immunity gene, and/or an immune inhibitory receptor gene. It is determined whether inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of the T cell infiltration-associated gene, receptor signaling gene, activation gene, or cytotoxicity gene in the test sample is higher than the level of the corresponding gene in the reference sample.

Suitable T cell infiltration-associated genes include cluster of differentiation 2 (CD2), CD6, and C-X-C motif chemokine ligand 13 (CXCL13). Exemplary receptor signaling genes include CD3D, CD3E, CD3G, lymphocyte-specific protein tyrosine kinase (LCK), T cell receptor alpha gene, T cell receptor beta gene, and PTCRA. Suitable activation genes include CD28, inducible t-cell co-stimulator (ICOS), eomesodermin (EOMES), interleukin-2 receptor subunit beta (IL2RB), Fas ligand (FASLG), and signaling lymphocytic activation molecule family member 6 (SLAMF6). In one aspect, cytotoxicity genes include granulysin (GNLY), granzyme A (GZMA), GZMB, GZMH, GZMK, and perforin 1 (PRF1). Suitable humoral immunity genes include CD19, CD72, Fc receptor-like protein 1/3 (FCRL1/3), and membrane spanning 4-domains A1 (MS4A1).

In some cases, immune inhibitory receptors include a receptor specific to or preferentially expressed by T cells such as CTLA4 and lymphocyte-activation gene-3 (LAG3). Alternatively, the immune inhibitory receptor comprises a receptor specific to or preferentially expressed by B cells such as CTLA4, FCRL1, and FCRL3. In other cases, the immune inhibitory receptor comprises a receptor specific to or preferentially expressed by macrophages such as CD5L. In other aspects, the immune inhibitory receptor comprises a receptor specific to or preferentially expressed by eosinophils/mast cells such as sialic acid-binding Ig-like lectin 8 (SIGLEC8). Alternatively, the immune inhibitory receptor comprises fas apoptotic inhibitory molecule 3 (FAIM3/TOSO).

In one aspect, the test sample is obtained from the melanoma and the melanoma-associated gene comprises CD2, CD6, CXCL13, CD3D, CD3E, CD3G, LCK, T cell receptor alpha gene, T cell receptor beta gene, CD28, ICOS, EOMES, IL2RB, FASLG, SLAMF6, GNLY, GZMA, GZMB, GZMH, GZMK, PRF1, PTCRA, CD19, CD72, FCRL1/3, MS4A1, CTLA4, LAG3, FCRL1, FCRL3, CD5L, SIGLEC8, and/or FAIM3/TOSO (or any combination thereof). It is determined that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of CD2, CD6, CXCL13, CD3D, CD3E, CD3G, LCK, T cell receptor alpha gene, T cell receptor beta gene, CD28, ICOS, EOMES, IL2RB, FASLG, SLAMF6, GNLY, GZMA, GZMB, GZMH, GZMK, PRF1, PTCRA, CD19, CD72, FCRL1/3, MS4A1, CTLA4, LAG3, FCRL1, FCRL3, CD5L, SIGLEC8, and/or FAIM3/TOSO (or any combination thereof) in the test sample is higher than the level of the corresponding gene in the reference sample.

Alternatively, the test sample is obtained from the melanoma and the melanoma-associated gene comprises miR-211, along with one or more of CD2, CD6, CXCL13, CD3D, CD3E, CD3G, LCK, T cell receptor alpha gene, T cell receptor beta gene, CD28, ICOS, EOMES, IL2RB, FASLG, SLAMF6, GNLY, GZMA, GZMB, GZMH, GZMK, PRF1, PTCRA, CD19, CD72, FCRL1/3, MS4A1, CTLA4, LAG3, FCRL1, FCRL3, CD5L, SIGLEC8, and/or FAIM3/TOSO (or any combination thereof). It is determined that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of miR-211, along with one or more of CD2, CD6, CXCL13, CD3D, CD3E, CD3G, LCK, T cell receptor alpha gene, T cell receptor beta gene, CD28, ICOS, EOMES, IL2RB, FASLG, SLAMF6, GNLY, GZMA, GZMB, GZMH, GZMK, PRF1, PTCRA, CD19, CD72, FCRL1/3, MS4A1, CTLA4, LAG3, FCRL1, FCRL3, CD5L, SIGLEC8, and/or FAIM3/TOSO (or any combination thereof) in the test sample is higher than the level of the corresponding gene in the reference sample.

Suitable samples include those with deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) therein. For example, the sample is a tumor sample. In anther aspect, the sample is a tumor microenvironment sample. Optionally, the sample is a plasma sample or a blood sample. In some cases, the sample comprises one or more circulating tumor cells.

In some cases, the reference sample is obtained from healthy normal tissue, melanoma that received a clinical benefit from CTLA4 inhibition, or melanoma that did not receive a clinical benefit from CTLA4 inhibition.

Optionally, the expression level of the melanoma-associated gene is detected via an Affymetrix Gene Array hybridization, next-generation sequencing, ribonucleic acid sequencing (RNA-seq), a real time reverse transcriptase polymerase chain reaction (real time RT-PCR) assay, immunohistochemistry (IHC), immunofluorescence, or methylation-specific PCR.

In one aspect, the expression level of the melanoma-associated gene is detected via RNA-seq and the reference sample is obtained from healthy normal tissue from the same individual as the test sample or one or more healthy normal tissues from different individuals.

In other cases, the expression level of the melanoma-associated gene is detected via RT-PCR and the reference sample is obtained from the same tissue as the test sample. In this case, levels of a housekeeping gene are determined in the reference sample. Suitable housekeeping genes include glyceraldehyde 3-phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1), and serine/threonine protein kinase (PSK1). The method involves determining whether CTLA4 blockade will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the expression level of the housekeeping gene.

The methods described herein optionally further comprise treating the subject with a chemotherapeutic agent, radiation therapy, cryotherapy, or hormone therapy. Exemplary chemotherapeutic agents include dacarbazine, temozolomide, nab-paclitaxel, paclitaxel, cisplatin, or carboplatin.

In some cases, the methods described herein further comprise administering an inhibitor of the melanoma-associated gene with a higher level of expression compared to the level of the melanoma-associated gene in the reference sample, thereby treating the melanoma. Suitable inhibitors include a small molecule inhibitor, RNA interference (RNAi), an antibody, an antibody fragment, an antibody drug conjugate, an aptamer, a chimeric antigen receptor (CAR), a T cell receptor, or any combination thereof.

In some cases, the antibody or antibody fragment is partially humanized, fully humanized, or chimeric. For example, the antibody fragment is a nanobody, an Fab, an Fab′, an (Fab′)2, an Fv, a single-chain variable fragment (ScFv), a diabody, a triabody, a tetrabody, a Bis-scFv, a minibody, an Fab2, an Fab3 fragment, or any combination thereof.

Alternatively, the methods described herein further comprise administering an agonist of the melanoma-associated gene with a higher level of expression compared to the level of the melanoma-associated gene in the reference sample, thereby treating the melanoma.

Optionally, the methods include administering to the subject a CTLA4 inhibitor, thereby treating the melanoma. For example, the CTLA4 inhibitor is an anti-CTLA4 antibody, e.g., ipilimumab or tremelimumab.

Also provided are compositions for predicting no clinical benefit in response to CTLA4 therapy comprising a melanoma-associated gene. For example, the melanoma-associated gene comprises MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, CSAG3, or CSAG4 synthesized complementary deoxyribonucleic acid (cDNA).

In some cases, the composition further comprises PSG1, PSG2, PSG4, PSG5, PSG6, GABRA3, GABRB1, GABRB2, GABRG2, GABRQ, GABRR1, CLDN1, CLDN2, EYA1, SNAI1, TGFB2, WNT3, HOXD13, HOXD11, HOXA2, HOXA5, HOXD10, ANGPT1, ANG2, PDGFA, PCDHB2, PCDHB3, PCDHB6, PCDHB10, PCDHGA3, PCDHGB1, PCDHGB2, EMILIN1, and/or TNN synthesized cDNA.

Also provided are compositions for predicting clinical benefit in response to CTLA4 therapy comprising miR-211 and a melanoma-associated gene selected from the group consisting of CD5L, IL12RB2, FAIM3, PTCRA, CD2, CD6, CXCL13, CD3D, CD3E, CD3G, LCK, T cell receptor alpha gene, T cell receptor beta gene, GNLY, GZMA, GZMB, GZMH, GZMK, PRF1, CD19, CD72, FCRL1/3, MS4A1, CTLA4, LAG3, FCRL1, FCRL3, SIGLEC8, and FAIM3/TOSO synthesized cDNA.

In one aspect, the melanoma-associated gene is immobilized on a solid support. Optionally, the melanoma-associated gene is linked to a detectable label. Exemplary detectable labels include a fluorescent label, a luminescent label, a chemiluminescent label, a radiolabel, a SYBR Green label, and a Cy3-label.

Preferably, the compositions comprising melanoma-associated genes include synthetic or non-naturally occurring melanoma-associated genes.

Provided is a method of treating cancer in a subject in need thereof, comprising: administering a therapeutically effective amount of one or more CTLA4 inhibitor agents to the subject, wherein the subject is identified as (a) not having aberrant expression of at least one resistant cancer-associated gene or miRNA, or (b) having aberrant expression of at least one beneficial cancer-associated gene or miRNA.

Also provided is a method of treating cancer in a subject in need thereof, comprising: (a) analyzing a biological sample from the subject for: (i) aberrant expression of at least one resistant cancer-associated gene or miRNA, wherein the aberrant expression of the at least one resistant cancer-associated gene or miRNA is not present in the biological sample, or (ii) aberrant expression of at least one beneficial cancer-associated gene or miRNA, wherein the aberrant expression of the at least one beneficial cancer-associated gene or miRNA is present in the biological sample; (b) identifying the subject as a candidate for receiving one or more CTLA4 inhibitor agents; and (c) administering a therapeutically effective amount of the one or more CTLA4 inhibitor agents to the subject.

The invention provides a method of identifying a subject with cancer as a candidate for receiving one or more CTLA4 inhibitor agents, comprising: (a) analyzing a biological sample from the subject for: (i) aberrant expression of at least one resistant cancer-associated gene or miRNA, wherein the aberrant expression of the at least one resistant cancer-associated gene or miRNA is not present in the biological sample, or (ii) aberrant expression of at least one beneficial cancer-associated gene or miRNA, wherein the aberrant expression of the at least one beneficial cancer-associated gene or miRNA is present in the biological sample; and (b) identifying the subject as a candidate for receiving one or more ctla4 inhibitor agents.

Also provided is a method to predict a response of a subject with cancer to a CTLA4 therapy, the method comprising: (a) assaying for (i) aberrant expression of at least one resistant cancer-associated gene or miRNA in a biological sample from the subject, wherein the aberrant expression of the at least one resistant cancer-associated gene or miRNA is not present in the biological sample, or (ii) aberrant expression of at least one beneficial cancer-associated gene or miRNA in a biological sample from the subject, wherein the aberrant expression of the at least one beneficial cancer-associated gene or miRNA is present in the biological sample; and (b) predicting a response of the subject with cancer to a CTLA4 therapy to be positive based on the assaying.

Described herein is a method of treating cancer comprising administering an effective amount of a CTLA4 inhibitor and an effective amount of an agonist (or inducer) of autophagy. For example, the CTLA4 inhibitor comprises ipilimumab or tremelimumab. In some cases, the autophagy agonist comprises metformin, temozolomide, trifluoperazine, divalproex sodium, vorinostat, rapamycin, everolimus, MG-132, doxorubicin, ABT-737, BCL2 inhibitors/antagonists, gemcitabine, torin 1, or resveratrol, etc.

Also provided herein are methods of determining whether administration of a CTLA4 inhibitor and an autophagy agonist to a subject with melanoma will result in clinical benefit in the subject comprising obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether administration of a CTLA4 inhibitor and an autophagy agonist will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample. For example, the autophagy agonist comprises metformin, temozolomide, trifluoperazine, divalproex sodium, vorinostat, rapamycin, everolimus, MG-132, doxorubicin, ABT-737, BCL2 inhibitors/antagonists, gemcitabine, torin 1, or resveratrol, etc.

In some cases, the test sample is obtained from the melanoma, wherein the melanoma-associated gene comprises a cancer germline antigen (CGA) gene; and the method comprises determining that administration of the CTLA4 inhibitor and the autophagy agonist in a subject with melanoma will result in clinical benefit in the subject if the expression level of the CGA gene in the test sample is higher than the level of the CGA gene in the reference sample. For example, the CGA gene comprises MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, or CSAG3.

Also provided are methods of treating cancer comprising administering an effective amount of a CTLA4 inhibitor and an effective amount of a agonist (or inducer) of miR-211, miR-185 and/or miR-513A2. For example, the CTLA4 inhibitor comprises ipilimumab or tremelimumab. In some cases, the agonist of miR-211, miR-185 and/or miR-513A2 comprises a miR mimetic (natural or synthetic) or aptamer.

Also provided are methods of determining whether administration of a CTLA4 inhibitor and a miR-211, miR-185, or miR-513A2) agonist to a subject with melanoma will result in clinical benefit in the subject comprising: obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether administration of a CTLA4 inhibitor and an miR-211, miR-185 and/or miR-513A2 agonist will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample. For example, the miR-211, miR-185 and/or miR-513A2 agonist comprises a miR mimetic (natural or synthetic) or aptamer.

In some cases, the test sample is obtained from the melanoma, wherein the melanoma-associated gene comprises a micro RNA gene; and determining that administration of the CTLA4 inhibitor and the miR-211, miR-185, and/or miR-513A2 agonist in a subject with melanoma will result in clinical benefit in the subject if the expression level of the miR-211, miR-513A2, or miR-185 in the test sample is higher than the level of the miR-211, miR-185 and/or miR-513A2 in the reference sample.

In other cases, the test sample is obtained from the melanoma, wherein the melanoma-associated gene comprises a melastatin-1 (TRPM1) gene; and determining that administration of the CTLA4 inhibitor and the miR-211, miR-185, and/or miR-513A2 agonist in a subject with melanoma will result in clinical benefit in the subject if the expression level of the TRPM1 gene in the test sample is higher than the level of the TRPM1 gene in the reference sample.

Provided herein are kits comprising reagents for assaying a biological sample from a subject with cancer for: (a) aberrant expression of at least one resistant cancer-associated gene or miRNA, or (b) aberrant expression of at least one beneficial cancer-associated gene or miRNA.

In one aspect, the aberrant expression of the at least one resistant cancer-associated gene or miRNA comprises overexpression of the at least one resistant cancer-associated gene or miRNA.

In another aspect, the aberrant expression of the at least one resistant cancer-associated gene is characterized by expression from a hypomethylated form of the at least one resistant cancer-associated gene.

In some cases, the aberrant expression of at least one beneficial cancer-associated gene or miRNA comprises overexpression of the at least one beneficial cancer-associated gene or miRNA.

Definitions

Unless specifically stated or obvious from context, as used herein, the term “about” is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean. “About” can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from context, all numerical values provided herein are modified by the term “about.”

The phrase “aberrant expression” is used to refer to an expression level that deviates from (i.e., an increased or decreased expression level) the normal reference expression level of the gene.

The term “antineoplastic agent” is used herein to refer to agents that have the functional property of inhibiting a development or progression of a neoplasm in a human, e.g., a melanoma. Inhibition of metastasis is frequently a property of antineoplastic agents.

By “agent” is meant any small compound, antibody, nucleic acid molecule, or polypeptide, or fragments thereof.

By “alteration” is meant a change (increase or decrease) in the expression levels or activity of a gene or polypeptide as detected by standard art-known methods such as those described herein. As used herein, an alteration includes at least a 1% change in expression levels, e.g., at least a 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% change in expression levels. For example, an alteration includes at least a 5%-10% change in expression levels, preferably a 25% change, more preferably a 40% change, and most preferably a 50% or greater change in expression levels.

By “ameliorate” is meant decrease, suppress, attenuate, diminish, arrest, or stabilize the development or progression of a disease.

The term “antibody” (Ab) as used herein includes monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity. The term “immunoglobulin” (Ig) is used interchangeably with “antibody” herein.

An “isolated antibody” is one that has been separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In preferred embodiments, the antibody is purified: (1) to greater than 95% by weight of antibody as determined by the Lowry method, and most preferably more than 99% by weight; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator; or (3) to homogeneity by SDS-PAGE under reducing or non-reducing conditions using Coomassie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step.

The basic four-chain antibody unit is a heterotetrameric glycoprotein composed of two identical light (L) chains and two identical heavy (H) chains. An IgM antibody consists of 5 of the basic heterotetramer unit along with an additional polypeptide called J chain, and therefore contain 10 antigen binding sites, while secreted IgA antibodies can polymerize to form polyvalent assemblages comprising 2-5 of the basic 4-chain units along with J chain. In the case of IgGs, the 4-chain unit is generally about 150,000 daltons. Each L chain is linked to an H chain by one covalent disulfide bond, while the two H chains are linked to each other by one or more disulfide bonds depending on the H chain isotype. Each H and L chain also has regularly spaced intrachain disulfide bridges. Each H chain has at the N-terminus, a variable domain (V_(H)) followed by three constant domains (C_(H)) for each of the α and γ chains and four C_(H) domains for μ and ε isotypes. Each L chain has at the N-terminus, a variable domain (V_(L)) followed by a constant domain (C_(L)) at its other end. The V_(L) is aligned with the V_(H) and the C_(L) is aligned with the first constant domain of the heavy chain (C_(H)1). Particular amino acid residues are believed to form an interface between the light chain and heavy chain variable domains. The pairing of a V_(H) and V_(L) together forms a single antigen-binding site. For the structure and properties of the different classes of antibodies, see, e.g., Basic and Clinical Immunology, 8th edition, Daniel P. Stites, Abba I. Terr and Tristram G. Parslow (eds.), Appleton & Lange, Norwalk, Conn., 1994, page 71, and Chapter 6.

The L chain from any vertebrate species can be assigned to one of two clearly distinct types, called kappa (κ) and lambda (λ), based on the amino acid sequences of their constant domains (C_(L)). Depending on the amino acid sequence of the constant domain of their heavy chains (C_(H)), immunoglobulins can be assigned to different classes or isotypes. There are five classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, having heavy chains designated alpha (α), delta (δ), epsilon (ε), gamma (γ) and mu (μ), respectively. The γ and α classes are further divided into subclasses on the basis of relatively minor differences in C_(H) sequence and function, e.g., humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The term “variable” refers to the fact that certain segments of the V domains differ extensively in sequence among antibodies. The V domain mediates antigen binding and defines specificity of a particular antibody for its particular antigen. However, the variability is not evenly distributed across the 110-amino acid span of the variable domains. Instead, the V regions consist of relatively invariant stretches called framework regions (FRs) of 15-30 amino acids separated by shorter regions of extreme variability called “hypervariable regions” that are each 9-12 amino acids long. The variable domains of native heavy and light chains each comprise four FRs, largely adopting a β-sheet configuration, connected by three hypervariable regions, which form loops connecting, and in some cases forming part of, the β-sheet structure. The hypervariable regions in each chain are held together in close proximity by the FRs and, with the hypervariable regions from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)). The constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, such as participation of the antibody in antibody dependent cellular cytotoxicity (ADCC).

The term “hypervariable region” when used herein refers to the amino acid residues of an antibody that are responsible for antigen binding. The hypervariable region generally comprises amino acid residues from a “complementarity determining region” or “CDR” (e.g., around about residues 24-34 (L1), 50-56 (L2) and 89-97 (L3) in the V_(L), and around about 31-35 (H1), 50-65 (H2) and 95-102 (H3) in the V_(H) when numbered in accordance with the Kabat numbering system; Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991)); and/or those residues from a “hypervariable loop” (e.g., residues 24-34 (L1), 50-56 (L2) and 89-97 (L3) in the V_(L), and 26-32 (H1), 52-56 (H2) and 95-101 (H3) in the V_(H) when numbered in accordance with the Chothia numbering system; Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)); and/or those residues from a “hypervariable loop”/CDR (e.g., residues 27-38 (L1), 56-65 (L2) and 105-120 (L3) in the V_(L), and 27-38 (H1), 56-65 (H2) and 105-120 (H3) in the V_(H) when numbered in accordance with the IMGT numbering system; Lefranc, M. P. et al. Nucl. Acids Res. 27:209-212 (1999), Ruiz, M. e al. Nucl. Acids Res. 28:219-221 (2000)). Optionally the antibody has symmetrical insertions at one or more of the following points 28, 36 (L1), 63, 74-75 (L2) and 123 (L3) in the V_(L), and 28, 36 (H1), 63, 74-75 (H2) and 123 (H3) in the V_(H) when numbered in accordance with AHo; Honneger, A. and Plunkthun, A. J. Mol. Biol. 309:657-670 (2001)).

By “germline nucleic acid residue” is meant the nucleic acid residue that naturally occurs in a germline gene encoding a constant or variable region. “Germline gene” is the DNA found in a germ cell (i.e., a cell destined to become an egg or in the sperm). A “germline mutation” refers to a heritable change in a particular DNA that has occurred in a germ cell or the zygote at the single-cell stage, and when transmitted to offspring, such a mutation is incorporated in every cell of the body. A germline mutation is in contrast to a somatic mutation which is acquired in a single body cell. In some cases, nucleotides in a germline DNA sequence encoding for a variable region are mutated (i.e., a somatic mutation) and replaced with a different nucleotide.

The term “monoclonal antibody” as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic site. Furthermore, in contrast to polyclonal antibody preparations that include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, the monoclonal antibodies are advantageous in that they may be synthesized uncontaminated by other antibodies. The modifier “monoclonal” is not to be construed as requiring production of the antibody by any particular method. For example, the monoclonal antibodies useful in the present invention may be prepared by the hybridoma methodology first described by Kohler et al., Nature, 256:495 (1975), or may be made using recombinant DNA methods in bacterial, eukaryotic animal or plant cells (see, e.g., U.S. Pat. No. 4,816,567). The “monoclonal antibodies” may also be isolated from phage antibody libraries using the techniques described in Clackson et al., Nature, 352:624-628 (1991) and Marks et al., J. Mol. Biol., 222:581-597 (1991), for example.

Monoclonal antibodies include “chimeric” antibodies in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity (see U.S. Pat. No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)). Also provided are variable domain antigen-binding sequences derived from human antibodies. Accordingly, chimeric antibodies of primary interest herein include antibodies having one or more human antigen binding sequences (e.g., CDRs) and containing one or more sequences derived from a non-human antibody, e.g., an FR or C region sequence. In addition, chimeric antibodies of primary interest herein include those comprising a human variable domain antigen binding sequence of one antibody class or subclass and another sequence, e.g., FR or C region sequence, derived from another antibody class or subclass. Chimeric antibodies of interest herein also include those containing variable domain antigen-binding sequences related to those described herein or derived from a different species, such as a non-human primate (e.g., Old World Monkey, Ape, etc). Chimeric antibodies also include primatized and humanized antibodies.

Furthermore, chimeric antibodies may comprise residues that are not found in the recipient antibody or in the donor antibody. These modifications are made to further refine antibody performance. For further details, see Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992).

A “humanized antibody” is generally considered to be a human antibody that has one or more amino acid residues introduced into it from a source that is non-human. These non-human amino acid residues are often referred to as “import” residues, which are typically taken from an “import” variable domain. Humanization is traditionally performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Reichmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting import hypervariable region sequences for the corresponding sequences of a human antibody. Accordingly, such “humanized” antibodies are chimeric antibodies (U.S. Pat. No. 4,816,567) wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species.

A “human antibody” is an antibody containing only sequences present in an antibody naturally produced by a human. However, as used herein, human antibodies may comprise residues or modifications not found in a naturally occurring human antibody, including those modifications and variant sequences described herein. These are typically made to further refine or enhance antibody performance.

An “intact” antibody is one that comprises an antigen-binding site as well as a C_(L) and at least heavy chain constant domains, C_(H) 1, C_(H) 2 and C_(H) 3. The constant domains may be native sequence constant domains (e.g., human native sequence constant domains) or amino acid sequence variant thereof. Preferably, the intact antibody has one or more effector functions. An “antibody fragment” comprises a portion of an intact antibody, preferably the antigen binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab′, F(ab′)₂, and Fv fragments; diabodies; linear antibodies (see U.S. Pat. No. 5,641,870; Zapata et al., Protein Eng. 8(10): 1057-1062 [1995]); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments.

The phrase “functional fragment or analog” of an antibody is a compound having qualitative biological activity in common with a full-length antibody. For example, a functional fragment or analog of an anti-IgE antibody is one that can bind to an IgE immunoglobulin in such a manner so as to prevent or substantially reduce the ability of such molecule from having the ability to bind to the high affinity receptor, Fc_(ε)RI.

Papain digestion of antibodies produces two identical antigen-binding fragments, called “Fab” fragments, and a residual “Fc” fragment, a designation reflecting the ability to crystallize readily. The Fab fragment consists of an entire L chain along with the variable region domain of the H chain (V_(H)), and the first constant domain of one heavy chain (C_(H) 1). Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of an antibody yields a single large F(ab′)₂ fragment that roughly corresponds to two disulfide linked Fab fragments having divalent antigen-binding activity and is still capable of cross-linking antigen. Fab′ fragments differ from Fab fragments by having additional few residues at the carboxy terminus of the C_(H)1 domain including one or more cysteines from the antibody hinge region. Fab′-SH is the designation herein for Fab′ in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab′)₂ antibody fragments originally were produced as pairs of Fab′ fragments that have hinge cysteines between them. Other chemical couplings of antibody fragments are also known.

The “Fc” fragment comprises the carboxy-terminal portions of both H chains held together by disulfides. The effector functions of antibodies are determined by sequences in the Fc region, which region is also the part recognized by Fc receptors (FcR) found on certain types of cells.

“Fv” is the minimum antibody fragment that contains a complete antigen-recognition and -binding site. This fragment consists of a dimer of one heavy- and one light-chain variable region domain in tight, non-covalent association. From the folding of these two domains emanate six hypervariable loops (three loops each from the H and L chain) that contribute the amino acid residues for antigen binding and confer antigen binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site.

“Single-chain Fv” also abbreviated as “sFv” or “scFv” are antibody fragments that comprise the V_(H) and V_(L) antibody domains connected into a single polypeptide chain. Preferably, the sFv polypeptide further comprises a polypeptide linker between the V_(H) and V_(L) domains that enables the sFv to form the desired structure for antigen binding. For a review of sFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994); Borrebaeck 1995, infra.

The term “diabodies” refers to small antibody fragments prepared by constructing sFv fragments (see preceding paragraph) with short linkers (about 5-10 residues) between the V_(H) and V_(L) domains such that inter-chain but not intra-chain pairing of the V domains is achieved, resulting in a bivalent fragment, i.e., fragment having two antigen-binding sites. Bispecific diabodies are heterodimers of two “crossover” sFv fragments in which the V_(H) and V_(L) domains of the two antibodies are present on different polypeptide chains. Diabodies are described more fully in, for example, EP 404,097; WO 93/11161; and Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

As used herein, an antibody that “internalizes” is one that is taken up by (i.e., enters) the cell upon binding to an antigen on a mammalian cell (e.g., a cell surface polypeptide or receptor). The internalizing antibody will of course include antibody fragments, human or chimeric antibody, and antibody conjugates. For certain therapeutic applications, internalization in vivo is contemplated. The number of antibody molecules internalized will be sufficient or adequate to kill a cell or inhibit its growth, especially an infected cell. Depending on the potency of the antibody or antibody conjugate, in some instances, the uptake of a single antibody molecule into the cell is sufficient to kill the target cell to which the antibody binds. For example, certain toxins are highly potent in killing such that internalization of one molecule of the toxin conjugated to the antibody is sufficient to kill the infected cell.

As used herein, an antibody is said to be “immunospecific,” “specific for” or to “specifically bind” an antigen if it reacts at a detectable level with the antigen, preferably with an affinity constant, K_(a), of greater than or equal to about 10⁴ M⁻¹, or greater than or equal to about 10⁵ M⁻¹, greater than or equal to about 10⁶ M⁻¹, greater than or equal to about 10⁷ M⁻¹, or greater than or equal to 10⁸ M⁻¹. Affinity of an antibody for its cognate antigen is also commonly expressed as a dissociation constant K_(D), and in certain embodiments, HuM2e antibody specifically binds to M2e if it binds with a K_(D) of less than or equal to 10⁻⁴ M, less than or equal to about 10⁻⁵ M, less than or equal to about 10⁻⁶ M, less than or equal to 10⁻⁷ M, or less than or equal to 10⁻⁸ M. Affinities of antibodies can be readily determined using conventional techniques, for example, those described by Scatchard et al. (Ann. N.Y. Acad. Sci. USA 51:660 (1949)).

Binding properties of an antibody to antigens, cells or tissues thereof may generally be determined and assessed using immunodetection methods including, for example, immunofluorescence-based assays, such as immuno-histochemistry (IHC) and/or fluorescence-activated cell sorting (FACS).

An antibody having a “biological characteristic” of a designated antibody is one that possesses one or more of the biological characteristics of that antibody which distinguish it from other antibodies. For example, in certain embodiments, an antibody with a biological characteristic of a designated antibody will bind the same epitope as that bound by the designated antibody and/or have a common effector function as the designated antibody. The term “antagonist” antibody is used in the broadest sense, and includes an antibody that partially or fully blocks, inhibits, or neutralizes a biological activity of an epitope, polypeptide, or cell that it specifically binds. Methods for identifying antagonist antibodies may comprise contacting a polypeptide or cell specifically bound by a candidate antagonist antibody with the candidate antagonist antibody and measuring a detectable change in one or more biological activities normally associated with the polypeptide or cell.

Antibody “effector functions” refer to those biological activities attributable to the Fc region (a native sequence Fc region or amino acid sequence variant Fc region) of an antibody, and vary with the antibody isotype. Examples of antibody effector functions include: C1q binding and complement dependent cytotoxicity; Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; down regulation of cell surface receptors (e.g., B cell receptor); and B cell activation.

By “binding to” a molecule is meant having a physicochemical affinity for that molecule.

By “control” or “reference” is meant a standard of comparison. In one aspect, as used herein, “changed as compared to a control” sample or subject is understood as having a level that is statistically different than a sample from a normal, untreated, or control sample. Control samples include, for example, cells in culture, one or more laboratory test animals, or one or more human subjects. Methods to select and test control samples are within the ability of those in the art. An analyte can be a naturally occurring substance that is characteristically expressed or produced by the cell or organism (e.g., an antibody, a protein) or a substance produced by a reporter construct (e.g, β-galactosidase or luciferase). Depending on the method used for detection, the amount and measurement of the change can vary. Determination of statistical significance is within the ability of those skilled in the art, e.g., the number of standard deviations from the mean that constitute a positive result.

“Detect” refers to identifying the presence, absence, or amount of the agent (e.g., a nucleic acid molecule, for example deoxyribonucleic acid (DNA) or ribonucleic acid (RNA)) to be detected.

By “detectable label” is meant a composition that when linked (e.g., joined—directly or indirectly) to a molecule of interest renders the latter detectable, via, for example, spectroscopic, photochemical, biochemical, immunochemical, or chemical means. Direct labeling can occur through bonds or interactions that link the label to the molecule, and indirect labeling can occur through the use of a linker or bridging moiety which is either directly or indirectly labeled. Bridging moieties may amplify a detectable signal. For example, useful labels may include radioactive isotopes, magnetic beads, metallic beads, colloidal particles, fluorescent labeling compounds, electron-dense reagents, enzymes (for example, as commonly used in an enzyme-linked immunosorbent assay (ELISA)), biotin, digoxigenin, or haptens. When the fluorescently labeled molecule is exposed to light of the proper wave length, its presence can then be detected due to fluorescence. Among the most commonly used fluorescent labeling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, p-phthaldehyde and fluorescamine. The molecule can also be detectably labeled using fluorescence emitting metals such as 152 Eu, or others of the lanthanide series. These metals can be attached to the molecule using such metal chelating groups as diethylenetriaminepentacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA). The molecule also can be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged molecule is then determined by detecting the presence of luminescence that arises during the course of chemical reaction. Examples of particularly useful chemiluminescent labeling compounds are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.

A “detection step” may use any of a variety of known methods to detect the presence of nucleic acid (e.g., methylated DNA) or polypeptide. The types of detection methods in which probes can be used include Western blots, Southern blots, dot or slot blots, and Northern blots.

As used herein, the term “diagnosing” refers to classifying pathology or a symptom, determining a severity of the pathology (e.g., grade or stage), monitoring pathology progression, forecasting an outcome of pathology, and/or determining prospects of recovery.

By the terms “effective amount” and “therapeutically effective amount” of a formulation or formulation component is meant a sufficient amount of the formulation or component, alone or in a combination, to provide the desired effect. For example, by “an effective amount” is meant an amount of a compound, alone or in a combination, required to ameliorate the symptoms of a disease, e.g., melanoma, relative to an untreated patient. The effective amount of active compound(s) used to practice the present invention for therapeutic treatment of a disease varies depending upon the manner of administration, the age, body weight, and general health of the subject. Ultimately, the attending physician or veterinarian will decide the appropriate amount and dosage regimen. Such amount is referred to as an “effective” amount.

The term “expression profile” is used broadly to include a genomic expression profile. Profiles may be generated by any convenient means for determining a level of a nucleic acid sequence, e.g., quantitative hybridization of microRNA, labeled microRNA, amplified microRNA, complementary/synthetic DNA (cDNA), etc., quantitative polymerase chain reaction (PCR), and ELISA for quantitation, and allow the analysis of differential gene expression between two samples. A subject or patient tumor sample is assayed. Samples are collected by any convenient method, as known in the art. According to some embodiments, the term “expression profile” means measuring the relative abundance of the nucleic acid sequences in the measured samples.

By “FDR” is meant False Discovery Rate. When performing multiple statistical tests, for example, in comparing the signal of two groups in multiple data features, there is an increasingly high probability of obtaining false positive results, by random differences between the groups that can reach levels that would otherwise be considered statistically significant. In some cases, in order to limit the proportion of such false discoveries, statistical significance is defined only for data features in which the differences reached a p-value (by two-sided t-test) below a threshold, which is dependent on the number of tests performed and the distribution of p-values obtained in these tests.

By “fragment” is meant a portion of a polypeptide or nucleic acid molecule. This portion contains, preferably, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. For example, a fragment may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids. However, the invention also comprises polypeptides and nucleic acid fragments, so long as they exhibit the desired biological activity of the full length polypeptides and nucleic acid, respectively. A nucleic acid fragment of almost any length is employed. For example, illustrative polynucleotide segments with total lengths of about 10,000, about 5000, about 3000, about 2,000, about 1,000, about 500, about 200, about 100, about 50 base pairs in length (including all intermediate lengths) are included in many implementations of this invention. Similarly, a polypeptide fragment of almost any length is employed. For example, illustrative polypeptide segments with total lengths of about 10,000, about 5,000, about 3,000, about 2,000, about 1,000, about 5,000, about 1,000, about 500, about 200, about 100, or about 50 amino acids in length (including all intermediate lengths) are included in many implementations of this invention.

“Hybridization” means hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleobases. For example, adenine and thymine are complementary nucleobases that pair through the formation of hydrogen bonds.

By “hybridize” is meant pair to form a double-stranded molecule between complementary polynucleotide sequences (e.g., a gene described herein), or portions thereof, under various conditions of stringency. (See, e.g., Wahl, G. M. and S. L. Berger (1987) Methods Enzymol. 152:399; Kimmel, A. R. (1987) Methods Enzymol. 152:507).

The terms “isolated,” “purified,” or “biologically pure” refer to material that is free to varying degrees from components which normally accompany it as found in its native state. “Isolate” denotes a degree of separation from original source or surroundings. “Purify” denotes a degree of separation that is higher than isolation.

A “purified” or “biologically pure” protein is sufficiently free of other materials such that any impurities do not materially affect the biological properties of the protein or cause other adverse consequences. That is, a nucleic acid or peptide of this invention is purified if it is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. Purity and homogeneity are typically determined using analytical chemistry techniques, for example, polyacrylamide gel electrophoresis or high performance liquid chromatography. The term “purified” can denote that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. For a protein that can be subjected to modifications, for example, phosphorylation or glycosylation, different modifications may give rise to different isolated proteins, which can be separately purified.

Similarly, by “substantially pure” is meant a nucleotide or polypeptide that has been separated from the components that naturally accompany it. Typically, the nucleotides and polypeptides are substantially pure when they are at least 60%, 70%, 80%, 90%, 95%, or even 99%, by weight, free from the proteins and naturally-occurring organic molecules with they are naturally associated.

By “isolated nucleic acid” is meant a nucleic acid that is free of the genes which flank it in the naturally-occurring genome of the organism from which the nucleic acid is derived. The term covers, for example: (a) a DNA which is part of a naturally occurring genomic DNA molecule, but is not flanked by both of the nucleic acid sequences that flank that part of the molecule in the genome of the organism in which it naturally occurs; (b) a nucleic acid incorporated into a vector or into the genomic DNA of a prokaryote or eukaryote in a manner, such that the resulting molecule is not identical to any naturally occurring vector or genomic DNA; (c) a separate molecule such as a synthetic cDNA, a genomic fragment, a fragment produced by polymerase chain reaction (PCR), or a restriction fragment; and (d) a recombinant nucleotide sequence that is part of a hybrid gene, i.e., a gene encoding a fusion protein. Isolated nucleic acid molecules according to the present invention further include molecules produced synthetically, as well as any nucleic acids that have been altered chemically and/or that have modified backbones. For example, the isolated nucleic acid is a purified cDNA or RNA polynucleotide. Isolated nucleic acid molecules also include messenger ribonucleic acid (mRNA) molecules.

By an “isolated polypeptide” is meant a polypeptide of the invention that has been separated from components that naturally accompany it. Typically, the polypeptide is isolated when it is at least 60%, by weight, free from the proteins and naturally-occurring organic molecules with which it is naturally associated. Preferably, the preparation is at least 75%, more preferably at least 90%, and most preferably at least 99%, by weight, a polypeptide of the invention. An isolated polypeptide of the invention may be obtained, for example, by extraction from a natural source, by expression of a recombinant nucleic acid encoding such a polypeptide; or by chemically synthesizing the protein. Purity can be measured by any appropriate method, for example, column chromatography, polyacrylamide gel electrophoresis, or by HPLC analysis.

The term “immobilized” or “attached” refers to a probe (e.g., nucleic acid or protein) and a solid support in which the binding between the probe and the solid support is sufficient to be stable under conditions of binding, washing, analysis, and removal. The binding may be covalent or non-covalent. Covalent bonds may be formed directly between the probe and the solid support or may be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules. Non-covalent binding may be one or more of electrostatic, hydrophilic, and hydrophobic interactions. Included in non-covalent binding is the covalent attachment of a molecule to the support and the non-covalent binding of a biotinylated probe to the molecule. Immobilization may also involve a combination of covalent and non-covalent interactions.

By “marker” is meant any protein or polynucleotide having an alteration in expression level or activity that is associated with a disease or disorder, e.g., melanoma.

By “melanoma-associated gene” is meant a nucleic acid associated with the pathogenesis of melanoma.

By “modulate” is meant alter (increase or decrease). Such alterations are detected by standard art-known methods such as those described herein.

The term, “normal amount” refers to a normal amount of a complex in an individual known not to be diagnosed with melanoma. The amount of the molecule can be measured in a test sample and compared to the “normal control level,” utilizing techniques such as reference limits, discrimination limits, or risk defining thresholds to define cutoff points and abnormal values (e.g., for melanoma). The “normal control level” means the level of one or more proteins (or nucleic acids) or combined protein indices (or combined nucleic acid indices) typically found in a subject known not to be suffering from melanoma. Such normal control levels and cutoff points may vary based on whether a molecule is used alone or in a formula combining other proteins into an index. Alternatively, the normal control level can be a database of protein patterns from previously tested subjects who did not convert to melanoma over a clinically relevant time horizon. In another aspect, the normal control level can be a level relative to a housekeeping gene.

The level that is determined may be the same as a control level or a cut off level or a threshold level, or may be increased or decreased relative to a control level or a cut off level or a threshold level. In some aspects, the control subject is a matched control of the same species, gender, ethnicity, age group, smoking status, body mass index (BMI), current therapeutic regimen status, medical history, or a combination thereof, but differs from the subject being diagnosed in that the control does not suffer from the disease in question or is not at risk for the disease.

Relative to a control level, the level that is determined may be an increased level. As used herein, the term “increased” with respect to level (e.g., expression level, biological activity level, etc.) refers to any % increase above a control level. The increased level may be at least or about a 1% increase, at least or about a 5% increase, at least or about a 10% increase, at least or about a 15% increase, at least or about a 20% increase, at least or about a 25% increase, at least or about a 30% increase, at least or about a 35% increase, at least or about a 40% increase, at least or about a 45% increase, at least or about a 50% increase, at least or about a 55% increase, at least or about a 60% increase, at least or about a 65% increase, at least or about a 70% increase, at least or about a 75% increase, at least or about a 80% increase, at least or about a 85% increase, at least or about a 90% increase, or at least or about a 95% increase, relative to a control level.

Relative to a control level, the level that is determined may be a decreased level. As used herein, the term “decreased” with respect to level (e.g., expression level, biological activity level, etc.) refers to any % decrease below a control level. The decreased level may be at least or about a 1% decrease, at least or about a 5% decrease, at least or about a 10% decrease, at least or about a 15% decrease, at least or about a 20% decrease, at least or about a 25% decrease, at least or about a 30% decrease, at least or about a 35% decrease, at least or about a 40% decrease, at least or about a 45% decrease, at least or about a 50% decrease, at least or about a 55% decrease, at least or about a 60% decrease, at least or about a 65% decrease, at least or about a 70% decrease, at least or about a 75% decrease, at least or about a 80% decrease, at least or about a 85% decrease, at least or about a 90% decrease, or at least or about a 95% decrease, relative to a control level.

Nucleic acid molecules useful in the methods of the invention include any nucleic acid molecule that encodes a polypeptide of the invention or a fragment thereof. Such nucleic acid molecules need not be 100% identical with an endogenous nucleic acid sequence, but will typically exhibit substantial identity, e.g., at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identity. Polynucleotides having “substantial identity” to an endogenous sequence are typically capable of hybridizing with at least one strand of a double-stranded nucleic acid molecule.

For example, stringent salt concentration will ordinarily be less than about 750 mM NaCl and 75 mM trisodium citrate, preferably less than about 500 mM NaCl and 50 mM trisodium citrate, and more preferably less than about 250 mM NaCl and 25 mM trisodium citrate. Low stringency hybridization can be obtained in the absence of organic solvent, e.g., formamide, while high stringency hybridization can be obtained in the presence of at least about 35% formamide, and more preferably at least about 50% formamide. Stringent temperature conditions will ordinarily include temperatures of at least about 30° C., more preferably of at least about 37° C., and most preferably of at least about 42° C. Varying additional parameters, such as hybridization time, the concentration of detergent, e.g., sodium dodecyl sulfate (SDS), and the inclusion or exclusion of carrier DNA, are well known to those skilled in the art. Various levels of stringency are accomplished by combining these various conditions as needed. In a preferred embodiment, hybridization will occur at 30° C. in 750 mM NaCl, 75 mM trisodium citrate, and 1% SDS. In a more preferred embodiment, hybridization will occur at 37° C. in 500 mM NaCl, 50 mM trisodium citrate, 1% SDS, 35% formamide, and 100 μg/ml denatured salmon sperm DNA (ssDNA). In a most preferred embodiment, hybridization will occur at 42° C. in 250 mM NaCl, 25 mM trisodium citrate, 1% SDS, 50% formamide, and 200 μg/ml ssDNA. Useful variations on these conditions will be readily apparent to those skilled in the art.

For most applications, washing steps that follow hybridization will also vary in stringency. Wash stringency conditions can be defined by salt concentration and by temperature. As above, wash stringency can be increased by decreasing salt concentration or by increasing temperature. For example, stringent salt concentration for the wash steps will preferably be less than about 30 mM NaCl and 3 mM trisodium citrate, and most preferably less than about 15 mM NaCl and 1.5 mM trisodium citrate. Stringent temperature conditions for the wash steps will ordinarily include a temperature of at least about 25° C., more preferably of at least about 42° C., and even more preferably of at least about 68° C. In a preferred embodiment, wash steps will occur at 25° C. in 30 mM NaCl, 3 mM trisodium citrate, and 0.1% SDS. In a more preferred embodiment, wash steps will occur at 42 C in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. In a more preferred embodiment, wash steps will occur at 68° C. in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. Additional variations on these conditions will be readily apparent to those skilled in the art. Hybridization techniques are well known to those skilled in the art and are described, for example, in Benton and Davis (Science 196:180, 1977); Grunstein and Hogness (Proc. Natl. Acad. Sci., USA 72:3961, 1975); Ausubel et al. (Current Protocols in Molecular Biology, Wiley Interscience, New York, 2001); Berger and Kimmel (Guide to Molecular Cloning Techniques, 1987, Academic Press, New York); and Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York.

By “neoplasia” is meant a disease or disorder characterized by excess proliferation or reduced apoptosis. Illustrative neoplasms for which the invention can be used include, but are not limited to pancreatic cancer, leukemias (e.g., acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute myelomonocytic leukemia, acute monocytic leukemia, acute erythroleukemia, chronic leukemia, chronic myelocytic leukemia, chronic lymphocytic leukemia), polycythemia vera, lymphoma (Hodgkin's disease, non-Hodgkin's disease), Waldenstrom's macroglobulinemia, heavy chain disease, and solid tumors such as sarcomas and carcinomas (e.g., fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, nile duct carcinoma, choriocarcinoma, seminoma, embryonal carcinoma, Wilm's tumor, cervical cancer, uterine cancer, testicular cancer, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, glioblastoma multiforme, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodenroglioma, schwannoma, meningioma, melanoma, neuroblastoma, and retinoblastoma).

As used herein, in one aspect, “next-generation sequencing” (NGS), also known as high-throughput sequencing, is the catch-all term used to describe a number of different sequencing methodologies including, but not limited to, Illumina® sequencing, Roche 454 Sequencing™, Ion Torrent™: Proton/personal genome machine (PGM) sequencing, and SOLiD sequencing. These recent technologies allow for sequencing DNA and RNA much more quickly and cheaply than the previously used Sanger sequencing. See, LeBlanc et al., 2015 Cancers, 7: 1925-1958, incorporated herein by reference; and Goodwin et al., 2016 Nature Reviews Genetics, 17: 333-351, incorporated herein by reference.

As used herein, “obtaining” as in “obtaining an agent” includes synthesizing, purchasing, or otherwise acquiring the agent.

Unless specifically stated or obvious from context, as used herein, the term “or” is understood to be inclusive. Unless specifically stated or obvious from context, as used herein, the terms “a”, “an”, and “the” are understood to be singular or plural.

The phrase “pharmaceutically acceptable carrier” is art recognized and includes a pharmaceutically acceptable material, composition or vehicle, suitable for administering compounds of the present invention to mammals. The carriers include liquid or solid filler, diluent, excipient, solvent or encapsulating material, involved in carrying or transporting the subject agent from one organ, or portion of the body, to another organ, or portion of the body. Each carrier must be “acceptable” in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials which can serve as pharmaceutically acceptable carriers include: sugars, such as lactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and its derivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppository waxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitol and polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents, such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; phosphate buffer solutions; and other non-toxic compatible substances employed in pharmaceutical formulations.

By “protein” or “polypeptide” or “peptide” is meant any chain of more than two natural or unnatural amino acids, regardless of post-translational modification (e.g., glycosylation or phosphorylation), constituting all or part of a naturally-occurring or non-naturally occurring polypeptide or peptide, as is described herein.

“Primer set” means a set of oligonucleotides that may be used, for example, for PCR. A primer set would consist of at least 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 30, 40, 50, 60, 80, 100, 200, 250, 300, 400, 500, 600, or more primers.

The terms “preventing” and “prevention” refer to the administration of an agent or composition to a clinically asymptomatic individual who is at risk of developing, susceptible, or predisposed to a particular adverse condition, disorder, or disease, and thus relates to the prevention of the occurrence of symptoms and/or their underlying cause.

The term “prognosis,” “staging,” and “determination of aggressiveness” are defined herein as the prediction of the degree of severity of the neoplasia, e.g., melanoma, and of its evolution as well as the prospect of recovery as anticipated from usual course of the disease. Once the aggressiveness (e.g. the Gleason score) has been determined, appropriate methods of treatments are chosen.

Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it is understood that the particular value forms another aspect. It is further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. It is also understood that throughout the application, data are provided in a number of different formats and that this data represent endpoints and starting points and ranges for any combination of the data points. For example, if a particular data point “10” and a particular data point “15” are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 as well as all intervening decimal values between the aforementioned integers such as, for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9. With respect to sub-ranges, “nested sub-ranges” that extend from either end point of the range are specifically contemplated. For example, a nested sub-range of an exemplary range of 1 to 50 may comprise 1 to 10, 1 to 20, 1 to 30, and 1 to 40 in one direction, or 50 to 40, 50 to 30, 50 to 20, and 50 to 10 in the other direction.

By “reduces” is meant a negative alteration of at least 10%, 25%, 50%, 75%, or 100%.

A “reference sequence” is a defined sequence used as a basis for sequence comparison or a gene expression comparison. A reference sequence may be a subset of or the entirety of a specified sequence; for example, a segment of a full-length cDNA or gene sequence, or the complete cDNA or gene sequence. For polypeptides, the length of the reference polypeptide sequence will generally be at least about 16 amino acids, preferably at least about 20 amino acids, more preferably at least about 25 amino acids, and even more preferably about 35 amino acids, about 50 amino acids, or about 100 amino acids. For nucleic acids, the length of the reference nucleic acid sequence will generally be at least about 40 nucleotides, preferably at least about 60 nucleotides, more preferably at least about 75 nucleotides, and even more preferably about 100 nucleotides or about 300 or about 500 nucleotides or any integer thereabout or there between.

The term “sample” as used herein refers to a biological sample obtained for the purpose of evaluation in vitro. Exemplary tissue samples for the methods described herein include tissue samples from melanoma tumors or the surrounding microenvironment (i.e., the stroma). With regard to the methods disclosed herein, the sample or patient sample preferably may comprise any body fluid or tissue. In some embodiments, the bodily fluid includes, but is not limited to, blood, plasma, serum, lymph, breast milk, saliva, mucous, semen, vaginal secretions, cellular extracts, inflammatory fluids, cerebrospinal fluid, feces, vitreous humor, or urine obtained from the subject. In some aspects, the sample is a composite panel of at least two of a blood sample, a plasma sample, a serum sample, and a urine sample. In exemplary aspects, the sample comprises blood or a fraction thereof (e.g., plasma, serum, fraction obtained via leukopheresis). Preferred samples are whole blood, serum, plasma, or urine. A sample can also be a partially purified fraction of a tissue or bodily fluid.

A reference sample can be a “normal” sample, from a donor not having the disease or condition fluid, or from a normal tissue in a subject having the disease or condition. A reference sample can also be from an untreated donor or cell culture not treated with an active agent (e.g., no treatment or administration of vehicle only). A reference sample can also be taken at a “zero time point” prior to contacting the cell or subject with the agent or therapeutic intervention to be tested or at the start of a prospective study.

A “solid support” describes a strip, a polymer, a bead, or a nanoparticle. The strip may be a nucleic acid-probe (or protein) coated porous or non-porous solid support strip comprising linking a nucleic acid probe to a carrier to prepare a conjugate and immobilizing the conjugate on a porous solid support. Well-known supports or carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, gabbros, and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material may have virtually any possible structural configuration so long as the coupled molecule is capable of binding to a binding agent (e.g., an antibody or nucleic acid molecule). Thus, the support configuration may be spherical, as in a bead, or cylindrical, as in the inside surface of a test tube, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, or test strip, etc. For example, the supports include polystyrene beads. Those skilled in the art will know many other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation. In other aspects, the solid support comprises a polymer, to which an agent is chemically bound, immobilized, dispersed, or associated. A polymer support may be a network of polymers, and may be prepared in bead form (e.g., by suspension polymerization). The location of active sites introduced into a polymer support depends on the type of polymer support. For example, in a swollen-gel-bead polymer support the active sites are distributed uniformly throughout the beads, whereas in a macroporous-bead polymer support they are predominantly on the internal surfaces of the macropores. The solid support, e.g., a device contains a binding agent alone or together with a binding agent for at least one, two, three or more other molecules.

By “specifically binds” is meant a compound or antibody that recognizes and binds a polypeptide of the invention, but which does not substantially recognize and bind other molecules in a sample, for example, a biological sample, which naturally includes a polypeptide of the invention.

A “specific binding agent” describes agents having greater than 10-fold, preferably greater than 100-fold, and most preferably, greater than 1000-fold affinity for the target molecule as compared to another molecule. As the skilled artisan will appreciate the term specific is used to indicate that other biomolecules present in the sample do not significantly bind to the binding agent specific for the target molecule. Preferably, the level of binding to a biomolecule other than the target molecule results in a binding affinity which is at most only 10% or less, only 5% or less only 2% or less or only 1% or less of the affinity to the target molecule, respectively. A preferred specific binding agent will fulfill both the above minimum criteria for affinity as well as for specificity. For example, an antibody has a binding affinity in the low micromolar (10⁻⁶), nanomolar (10⁻⁷-10⁻⁹), with high affinity antibodies in the low nanomolar (10⁻⁹) or pico molar (10⁻¹²) range for its specific target molecule.

By “substantially identical” is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). Preferably, such a sequence is at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical at the amino acid level or nucleic acid to the sequence used for comparison.

Sequence identity is typically measured using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705, BLAST, BESTFIT, GAP, or PILEUP/PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and/or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, a BLAST program may be used, with a probability score between e⁻³ and e⁻¹⁰⁰ indicating a closely related sequence.

The term “subject” as used herein includes all members of the animal kingdom prone to suffering from the indicated disorder. In some aspects, the subject is a mammal, and in some aspects, the subject is a human. The methods are also applicable to companion animals such as dogs and cats as well as livestock such as cows, horses, sheep, goats, pigs, and other domesticated and wild animals.

A subject “suffering from or suspected of suffering from” a specific disease, condition, or syndrome has a sufficient number of risk factors or presents with a sufficient number or combination of signs or symptoms of the disease, condition, or syndrome such that a competent individual would diagnose or suspect that the subject was suffering from the disease, condition, or syndrome. Methods for identification of subjects suffering from or suspected of suffering from conditions associated with cancer (e.g., melanoma) is within the ability of those in the art. Subjects suffering from, and suspected of suffering from, a specific disease, condition, or syndrome are not necessarily two distinct groups.

As used herein, “susceptible to” or “prone to” or “predisposed to” or “at risk of developing” a specific disease or condition refers to an individual who based on genetic, environmental, health, and/or other risk factors is more likely to develop a disease or condition than the general population. An increase in likelihood of developing a disease may be an increase of about 10%, 20%, 50%, 100%, 150%, 200%, or more.

The terms “treating” and “treatment” as used herein refer to the administration of an agent or formulation to a clinically symptomatic individual afflicted with an adverse condition, disorder, or disease, so as to effect a reduction in severity and/or frequency of symptoms, eliminate the symptoms and/or their underlying cause, and/or facilitate improvement or remediation of damage. It will be appreciated that, although not precluded, treating a disorder or condition does not require that the disorder, condition or symptoms associated therewith be completely eliminated.

As used herein, in one aspect, the “tumor microenvironment” (TME) is the cellular environment in which a tumor exists, including surrounding blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells, such as in immuno-editing.

In some cases, a composition of the invention is administered orally or systemically. Other modes of administration include rectal, topical, intraocular, buccal, intravaginal, intracisternal, intracerebroventricular, intratracheal, nasal, transdermal, within/on implants, or parenteral routes. The term “parenteral” includes subcutaneous, intrathecal, intravenous, intramuscular, intraperitoneal, or infusion. Intravenous or intramuscular routes are not particularly suitable for long-term therapy and prophylaxis. They could, however, be preferred in emergency situations. Compositions comprising a composition of the invention can be added to a physiological fluid, such as blood. Oral administration can be preferred for prophylactic treatment because of the convenience to the patient as well as the dosing schedule. Parenteral modalities (subcutaneous or intravenous) may be preferable for more acute illness, or for therapy in patients that are unable to tolerate enteral administration due to gastrointestinal intolerance, ileus, or other concomitants of critical illness. Inhaled therapy may be most appropriate for pulmonary vascular diseases (e.g., pulmonary hypertension).

Pharmaceutical compositions may be assembled into kits or pharmaceutical systems for use in arresting cell cycle in rapidly dividing cells, e.g., cancer cells. Kits or pharmaceutical systems according to this aspect of the invention comprise a carrier means, such as a box, carton, tube, having in close confinement therein one or more container means, such as vials, tubes, ampoules, bottles, syringes, or bags. The kits or pharmaceutical systems of the invention may also comprise associated instructions for using the kit.

Any compositions or methods provided herein can be combined with one or more of any of the other compositions and methods provided herein.

Any compositions or methods provided herein can be combined with one or more of any of the other compositions and methods provided herein.

The transitional term “comprising,” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. By contrast, the transitional phrase “consisting of” excludes any element, step, or ingredient not specified in the claim. The transitional phrase “consisting essentially of” limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention.

Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All published foreign patents and patent applications cited herein are incorporated herein by reference. Genbank and NCBI submissions indicated by accession number cited herein are incorporated herein by reference. All other published references, documents, manuscripts and scientific literature cited herein are incorporated herein by reference. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A-FIG. 1C is a series of graphs showing transcriptomic signatures of resistance to CTLA4 blockade. FIG. 1A is a volcano plot depicting 975 genes enriched in NB tumors and 428 enriched genes in CB tumors. Relative positions of Xq28-CGAs, miR-211, TRPM1, and immune-related genes are shown. FIG. 1B is a graph showing a 75 Kb region within the Xq28 locus containing the 8 CGAs. Bar plots depicting the individual fold changes for each MAGE-A and CSAG gene within this locus are shown for RNA seq in discovery cohort (FIG. 1B (top)) and independent cohort (FIG. 1B (middle)). FIG. 1B (bottom) shows qPCR validation of expression of Xq28-CGA genes in benefit (n=10) and no-benefit (n=11) samples; fold changes are shown relative to HPRT1 gene. FIG. 1C is a graph showing that genes co-enriched with Xq28-CGA expression in TCGA significantly overlap with genes associated with NB tumors.

FIG. 2A is a volcano plot depicting genes enriched in ‘no progressive disease’ (No PD) and ‘progressive disease’ (PD) groups at week 13 in the ipilimumab-nivolumab arm of the CheckMate 064 trial (Weber et al., 2016) (validation cohort). FIG. 2B is a series of box plots depicting RNA-seq expression for CRMA MAGEA genes between the No PD and PD groups in validation cohort. FIG. 2C is a bar graph showing IHC staining analysis of MAGE-A protein expression in pre-ipilimumab melanoma biopsies. FIG. 2D is a photomicrograph showing examples of MAGE-A protein expression from a patient in the CB (left) and NB (right) groups. Magnification, ×1000.

FIG. 3A-FIG. 3B is a series of graphs that show DNA methylation patterns in resistant tumors and Xq28-high TCGA samples. FIG. 3A shows that MAGEA3 and MAGEA6 promoters in ‘no benefit’ patients (n=3) are preferentially de-methylated compared to ‘clinical benefit’ patients (n=3) as validated by bisulfite PCR. The plot highlights the local regression (solid line) of the mean methylation for every CpG (dots) along the MAGEA3 and MAGEA6 promoter in CB versus NB patients. The standard deviation is indicated by the shaded area. Note that both promoter sequences are identical within the analyzed amplicon span. FIG. 3B is a volcano plot of differentially methylated probes with false discovery rate <0.05 across the genome between Xq28 low and Xq28 high expression groups in the TCGA melanoma cohort.

FIG. 4A-FIG. 4E is a series of graphs showing transcriptomic signatures of clinical benefit to CTLA4 blockade. FIG. 4A is a series of bar plots depicting the individual fold changes for miR-211, TRPM1, and other TRPM family members. FIG. 4B is a bar graph of percentage of differentially expressed genes related to immune response, as determined by self-curation in both NB and CB tumors. FIG. 4C is a graph showing that genes associated with clinical benefit significantly overlap with genes co-enriched with miR-211 expression in TCGA but not with genes inversely associated with miR-211 expression. FIG. 4D is a graph showing that miR-211, miR-185 and miR-513A2 are significantly upregulated in clinical benefit tumors. FIG. 4E is a graph that shows proliferative gene expression signatures are significantly enriched in clinical benefit tumors, while the invasive gene expression signatures are significantly enriched in no benefit tumors.

FIG. 5A-FIG. 5B are a series of graphs showing that molecular signatures of outcome to CTLA4 blockade are unique and do not predict outcome to PD1 blockade. Specifically, FIG. 5A and FIG. 5B are barplots of fold changes for individual Xq28-CGAs, miR-211 and TRPM1 in pretreatment melanoma samples from responding and nonresponding patients to PD1 blockade. FIG. 5C is a series of box plots of RNA-seq expression values for each MAGEA gene in the CRMA locus within no progressive disease (no PD; blue) (n=23) and progressive disease (PD; orange) (n=14) pre-nivolumab melanoma tumors from CheckMate 064 (Weber et al., 2016).

FIG. 6A-FIG. 6C is a series of graphs showing that Xq28-CGA antigen and miR-211 predict outcome to CTLA4 blockade. FIG. 6A is a graph showing correlation of Xq28 CT antigen and miR-211 expression for all 40 patients in discovery cohort including NB, CB and “long term survival with no clinical benefit.” FIG. 6B is a graph showing ROC analysis comparing neoantigen load, CTLA4 expression, combined neoantigen load+CTLA4 expression, combined “Xq28-CGA+miR-211” expression, and a combination of all four parameters for all patients. FIG. 6C is a graph showing overall survival Kaplan-Meier curves for combination “neoantigen load+CTLA4 (left),” “Xq28-CGA+miR-211 (middle)” and “Xq28-CGA+miR-211+neoantigen load+CTLA4 (right).” FIG. 6D is Kaplan-Meier overall survival analysis comparing patients from discovery cohort classified by expression of MAGE-A protein. FIG. 6E is a table showing the Cox proportional hazards model of risk factors for outcomes after ipilimumab therapy. FIG. 6F is a graph showing the Kaplan-Meier overall survival analysis of TCGA melanoma samples with high or low expression of Xq28-CGA genes.

FIG. 7 is a series of graphs showing qPCR validation of Xq28-CGA genes using different housekeeping genes. Barplots showing similar fold changes of Xq28 genes from qPCR using either GAPDH (top) or PGK1 (bottom) as housekeeping genes.

FIG. 8 a series of graphs showing copy number analysis of Xq28 region in Clinical Benefit/No Benefit patients. Neither the locus average of copy ratios, nor copy ratios on individual targets showed a statistically significant germline or somatic variation between the two groups at 5% level.

FIG. 9 is a bar graph showing that DTIC/temozolamide treatment history does not affect outcome after ipilimumab. Patients were grouped into “DTIC” cohort if DTIC or temozolamide were used as treatment any timepoint before ipilimumab.

FIG. 10A-FIG. 10B is a series of graphs showing that gender and purity do not affect outcome after ipilimumab. Barplots of gender and purity comparing CB and NB groups showing no effect.

FIG. 11A-FIG. 11D is a series of graphs that show that MAGE-A proteins may degrade the danger molecule HMGB1. FIG. 11A is a bar graph showing the results of an in vitro screen for MAGE-TRIM28 ubiquitination substrates identifies HMGB1 (p<0.05). FIG. 11B is a series of photomicrographs with immunofluorescence staining for MAGE-A and HMGB1 showing mutual exclusion in five patient samples from the discovery cohort in addition to a human xenograft melanoma. Magnification ×400. FIG. 11C is a bar graph showing the percentage of differentially expressed genes related to immune response, in both NB (3.5%) and CB (56%) tumors. FIG. 11D is a graph showing gene set enrichment analysis of immune gene sets showing p-value of enrichment (signed according to enrichment score). Dashed line represents p=0.05.

FIG. 12A-FIG. 12D is a series of graphs showing that Xq28-CGA genes are upregulated in ipilimumab-resistant melanoma samples. FIG. 12A is a heatmap showing relative expression of Xq28-CGA genes for CB and NB patients in the discovery cohort with annotations for gender, purity and RECIST response. FIG. 12B is a heatmap showing relative expression of Xq28-CGA genes in the validation set (CheckMate 064) with annotations for gender and RECIST response. FIG. 12C is a series of box plots depicting the individual fold changes for each MAGEA gene within the Xq28-CGA locus for patients with no progressive (“no PD”) or progressive disease (“PD”) in the discovery cohort; p-values using the Wilcoxon test.

FIG. 13A is a graph showing that bisulfite PCR of unique methylation sites within the gene bodies of MAGEA3/A6/A12 genes highlights a slight to moderate decrease in methylation in NB patients (n=4, orange) vs. CB patients (n=4, blue). The position of 3 PCR amplicons are highlighted, and the plots highlight the mean methylation for each CpG within the amplicon region. FIG. 13B is a graph showing chromosomal locations of 65,467 hypomethylated (top) and 47 hypermethylated (bottom) probes in “CRMA-high” TCGA melanoma samples.

FIG. 14 is a graph showing biological processes enriched in NB transcriptomes. Specifically, FIG. 14 is a heatmap showing relative gene expression of NB-enriched biological categories (see Table 2) along with lack of enrichment of NY-ESO-1 and melanoma differentiation antigens. Annotations of gender, purity and RECIST response included.

FIG. 15A and FIG. 15B are graphs of immunofluorescence staining on a melanoma tissue mnicroarray (TMA) comprising 100 samples (9 benign nevi tumors, 91 primary and metastatic melanomas) using antibodies against MAGE and HMG3B. The fraction of HMGB1 positive cells were comparable in MAGE negative cells from the benign nevi and malignant tumors, but was significantly reduced in cells from MAGE+ malignant samples ((26% and 31% vs 8%, Chi-square test p<2.2×10⁻¹⁶ FIG. 15A). FIG. 15B is a graph showing that in 13 out of 15 melanomas (stained on the TMA) that had any MAGE positive cells, at least 85% of MAGE+ cells lack HMGB1 (FIG. 15B).

FIG. 16 is a graph showing the significant overexpression of genes, TLR9 and IL12A, in the clinical benefit tumors. These genes are downstream of the HMGB1 pathway and show this pathway is activated.

FIG. 17A is a graph showing significantly decreased autophagy (indicated by LC3B positive staining) in MAGE-A+ melanomas on a tissue microarray by immunohistochemistry. FIG. 17B is a graph showing significantly impaired autophagy (indicated by absent LC3B staining or double-positive LC3B/p62 staining) in MAGE-A+ melanomas.

DETAILED DESCRIPTION OF THE INVENTION

The invention is based, at least in part, upon the identification of a gene expression signature that discriminates clinical outcomes of CTLA4 blockade. CTLA4 blockade can induce durable clinical remissions in a minority of patients with metastatic melanoma. However, prior to the invention described herein, molecular signatures precisely predicting response and resistance were unknown. While increased neoantigen burden and clonality as well as increased expression of immune-related genes correlate with response, prior to the invention described herein, these molecular signatures were not clinically robust. Moreover, mechanistic insight into clinical resistance was lacking, and prior to the invention described herein, the contribution of epigenetic mechanisms was poorly understood.

Ipilimumab is an FDA-approved antibody targeting the CTLA4 pathway. Ipilimumab was the first agent to show an overall survival benefit in metastatic melanoma. However, only 15-20% of patients benefit from ipilimumab treatment. Prior to the invention described herein, there was no way to predict clinical outcome. Because ipilimumab carries significant autoimmune toxicity, predicting who will and will not benefit is of critical clinical importance. Ipilimumab is falling out of clinical use with the approval of newer, less toxic immunotherapies; however, long term survival data is only available for this agent. Thus, the results presented herein allow for precisely pairing CTLA4 blockade therapy with the appropriate patient.

Briefly, transcriptomic and clinical data from three independent melanoma cohorts were analyzed to identify correlates of outcome to CTLA4 blockade: (i) Cohort 1 comprised 40 pre-ipilimumab tumor samples (discovery set); (ii) Cohort 2 comprised 6 pre-treatment (ipilimumab or tremelimumab) samples (validation set 1); and (iii) Cohort 3 comprised 473 melanoma samples from The Cancer Genome Atlas (validation set 2). As described herein, genes that were differentially expressed between the clinical benefit (CB) and no clinical benefit (NB) groups were identified using unadjusted Wilcoxon tests (p<0.05), and a two-fold over-expression threshold in either group. The hypergeometric test was used to evaluate overlap of differentially expressed genes between cohorts, and the single-sample gene set enrichment (ssGSEA) method to identify pathway-level differences. Moreover, TCGA melanoma samples with high expression of the Xq28 CGA locus exhibited profound global hypomethylation, implicating epigenomic dysregulation and overexpression of Xq28 CGAs in primary resistance to CTLA4 blockade. Methylation-specific PCR of specific methylation sites of MAGE-A2, MAGE-A3, and MAGE-A12 revealed decreased methylation at these sites in nonresponding (vs. responding) tumors.

As described in detail below, 7 of the top 10 genes overexpressed in primary resistant tumors were cancer-germline antigens (CGA's), ranging from 60-180 fold enrichment. All 7 CGA's clustered tightly together within a narrow 75 kb region of chromosome Xq28. This pattern was clinically validated in Cohort 2 where this specific CGA cluster was similarly enriched in primary resistant tumors. Importantly, this pattern was biologically validated by finding that genes associated with clinical resistance from Cohort 1 significantly overlapped with genes associated with Xq28-CGA cluster expression in The Cancer Genome Atlas (TCGA) melanoma samples, further supporting the association of Xq28 expression with clinical resistance. As described in detail below, TCGA melanoma samples with high expression of the Xq28 CGA locus exhibited profound global hypomethylation, implicating epigenomic dysregulation and overexpression of Xq28 cancer testis antigen (CTA) in primary resistance to CTLA4 blockade.

Moreover, as described in detail below, in patients with clinical benefit, microRNA-211 was enriched over 700-fold, with statistically significant overlap observed between genes associated with clinical response and those associated with miR-211 in TCGA. The Xq28 associated CGA and miR-211 expression signatures were unique to CTLA4 blockade and did not predict outcome to anti-PD1 therapy. Expression levels of Xq28 associated CGAs and miR-211 predicted clinical outcome with 100% sensitivity and 40% specificity, outperforming previously identified correlates of benefit (ROC curve AUC=0.85). Expression of a coordinately transcribed cluster of 7 cancer germline antigens on chromosome Xq28 and miR-211 was strongly associated with resistance and response to anti-CTLA4 therapy respectively in metastatic melanoma. Thus, evaluation of transcriptional activity of these genes informs therapeutic preference in this disease.

Antibodies targeting the CTLA4 pathway in advanced melanoma have yielded durable clinical benefit in a minority of patients. Moreover, the combination of CTLA4 blockade with antagonists to another “immune checkpoint,” the programmed death (PD-1) pathway, increases response rates in metastatic melanoma compared with either agent alone, suggesting the potential for combining CTLA4 blockade with other immunotherapeutics. However, prior to the invention described herein, robust determinants of response and resistance to CTLA4 blockade were elusive, hindering efforts to rationally combine it with other therapies and precisely pair it with patients likely to respond.

Several investigators have identified genomic and transcriptional markers, such as the overall number of somatic mutations, number and clonality of tumor-specific “neoantigens,” and expression of immune genes, to correspond with response. However, the extensive overlap of these molecular signatures between responding and nonresponding tumors precludes their use in predicting clinical outcome. In preclinical studies, epigenetic programs have modulated response to anti-CTLA4 therapy, but prior to the invention described herein, they have not been investigated in large clinical cohorts. To date, discovery of robust predictive molecular signatures have been limited by sample size and lack of validation cohorts. As described in detail below, to interrogate and identify non-genomic determinants of clinical outcome to CTLA4 blockade in advanced melanoma, transcriptomic data from two previously reported clinical treatment cohorts as well as transcriptomic and DNA methylation data from The Cancer Genome Atlas (TCGA) was aggregated and analyzed.

Both as monotherapy and in combination with PD-1 blockade, anti-CTLA4 antibodies have induced substantial clinical benefit in melanoma; yet, prior to the invention described herein, robust molecular signatures of clinical outcome were elusive. Moreover, insight into mechanisms of primary clinical resistance was lacking. Knowledge of both is critical given the increasing evaluation of CTLA4 blockade in hematologic malignancies and the need to both rationally design combinatorial strategies as well as identify new immunotherapeutic targets. Here, the importance of in situ transcriptomic analyses to uncover immunotherapeutically relevant biology was revealed.

In particular, as described in detail below, a critical genomic locus on Xq28 that harbors a coordinately regulated cluster of CT antigens was identified. The striking enrichment of these genes with primary resistance affirms their status as a recent therapeutic target; the encoded proteins have been implicated in the ubiquitination of key tumor suppressors—notably TP53 and AMPK—that contributed to oncogenesis. In fact, these CT antigens specifically cluster in an inverted repeat DNA structure on Xq28, in which they are expressed coordinately and independently from CT antigens outside of this cluster. Thus, the finding that all of these genes appear as the most upregulated genes in resistant tumors reinforces their relevance as a genomic unit to clinical outcome to CTLA4 blockade.

As described in detail below, a co-enrichment of immunosuppressive pathways was identified along with these CT antigens, including the PSG genes as well as the GABA A receptor, which was recently implicated in attenuating T cell priming—a process also governed by the CTLA4 pathway. Associated immunosuppression may explain the long history of failed immunotherapeutic approaches targeting CT antigens such as MAGEA3 and MAGEA6 that lie within the Xq28 locus. The finding of multiple genes involved in epithelial-to-mesenchymal transition (EMT) is consistent with preclinical data suggesting EMT as an immunoevasive pathway employed by melanomas. Moreover, using TCGA data, global hypomethylation patterns were identified that strongly associated with high expression of CTA's from the Xq28 locus, implicating epigenomic mechanisms of resistance to CTLA4 blockade.

In responding tumors, the analysis revealed enrichment of the melanoma-suppressive miR-211 and a diversity of immune effectors, including T cells, B cells, macrophages, and eosinophils. miR-211 has been shown to inhibit TGF-beta signaling members (which were upregulated in resistant tumors), suppress the EMT phenotype, and mitigate the invasive phenotype. An increased number of genes mapping to both T cell and B cell receptors were identified, implicating an active adaptive immune response that appears to be diverse in its antigen recognition.

Although statistical stringency was relaxed because of the small cohort, the converging results from alternative cohorts bolster the results presented herein. Given that CTLA4 blockade may impact immune priming as opposed to the effector arm (influenced by the PD1 pathway), the results presented herein shed light into the mechanisms governing response/resistance to therapeutic manipulation of immune priming. The results presented herein indicate that response/resistance mechanisms to immune priming differ substantially from those relevant to clinical manipulation of effector immunity. As immunotherapeutic combinations are increasingly evaluated, understanding these mechanisms are important for precisely pairing patients with the appropriate combinations to avoid toxicity and ensure efficacy. The gene signatures described herein are potential therapeutic targets to sensitize to or combine with CTLA4 blockade.

Moreover, precisely pairing patients with cancer to the appropriate immunotherapy would reduce toxicity and costs as well as accelerate drug development. While ipilimumab as a single agent can induce durable tumor remissions in metastatic melanoma, only about 15-20% of patients with melanoma will benefit. Thus the majority of patients with melanoma are already resistant to ipilimumab. The results presented herein not only suggest a combination of immunotherapies that would raise this response rate, but they identify a signature to select those patients that would benefit from the combination (e.g. CTLA4 blockade+HMGB1 receptor agonist; or CTLA4 blockade+Xq28-CGA antagonist) over monotherapy. For example, a patient with high expression of the CGA gene would be assigned to the CTLA4 blockade+HMGB1 receptor agonist combination (or CTLA4 blockade+Xq28-CGA antagonist combination), whereas a patient with low expression of the CGA gene would be assigned to anti-CTLA4 monotherapy.

Melanoma

Cancer starts when cells in the body begin to grow out of control. Cells in nearly any part of the body can become cancer, and can then spread to other areas of the body. Melanoma is a cancer that usually starts in a certain type of skin cell, i.e., melanocytes. Melanocytes make a brown pigment called melanin, which gives the skin its tan or brown color. Melanin protects the deeper layers of the skin from some of the harmful effects of the sun. For most people, when skin is exposed to the sun, melanocytes make more melanin, causing the skin to tan or darken.

Other names for “melanoma” include malignant melanoma and cutaneous melanoma. Most melanoma cells still make melanin, so melanoma tumors are usually brown or black. However, some melanomas do not make melanin and can appear pink, tan, or even white. Melanomas can develop anywhere on the skin, but they are more likely to start on the trunk (chest and back) in men and on the legs in women. The neck and face are other common sites. Having darkly pigmented skin lowers the risk of melanoma at these more common sites, but anyone can get melanoma on the palms of the hands, soles of the feet, and under the nails. Melanomas can also form in other parts of the body such as the eyes, mouth, genitals, and anal area, but these are much less common than melanoma of the skin. Melanoma is much less common than basal cell and squamous cell skin cancers. However, melanoma is more dangerous because it is much more likely to spread to other parts of the body if not caught early.

The primary cause of melanoma is ultraviolet light (UV) exposure in those with low levels of skin pigment. The UV light may be from either the sun or from other sources, such as tanning devices. About 25% develop from moles. Those with many moles, a history of affected family members, and who have poor immune function are at greater risk. A number of rare genetic defects such as xeroderma pigmentosum also increase risk. Avoiding UV light and the use of sunscreen may prevent melanoma.

Melanoma may spread to other sites in the body by metastais. Metastatic melanoma may cause nonspecific paraneoplastic symptoms, including loss of appetite, nausea, vomiting and fatigue. Metastasis of early melanoma is possible, but relatively rare: less than a fifth of melanomas diagnosed early become metastatic. Brain metastases are particularly common in patients with metastatic melanoma. Melanoma may also spread to the liver, bones, abdomen or distant lymph nodes.

Melanoma Diagnosis

Visual inspection is the most common diagnostic technique. Moles that are irregular in color or shape are typically treated as candidates. To detect melanomas (and increase survival rates), it is recommended to regularly examine moles for changes (shape, size, color, itching or bleeding) and to consult a qualified physician when a candidate appears.

Early signs of melanoma are changes to the shape or color of existing moles or, in the case of nodular melanoma, the appearance of a new lump anywhere on the skin. At later stages, the mole may itch, ulcerate or bleed. Early signs of melanoma are summarized by the mnemonic “ABCDE”:

-   -   Asymmetry     -   Borders (irregular with edges and corners)     -   Color (variegated)     -   Diameter (greater than 6 mm (0.24 in), about the size of a         pencil eraser)     -   Evolving over time

These classifications do not, however, apply to the most dangerous form of melanoma, nodular melanoma, which has its own classifications:

-   -   Elevated above the skin surface     -   Firm to the touch     -   Growing

Following a visual examination and a dermatoscopic exam, or in vivo diagnostic tools such as a confocal microscope, the doctor may biopsy the suspicious mole. A skin biopsy performed under local anesthesia is often required to assist in making or confirming the diagnosis and in defining severity. Elliptical excisional biopsies may remove the tumor, followed by histological analysis and Breslow scoring. Punch biopsies are contraindicated in suspected melanomas, for fear of seeding tumor cells and hastening the spread of malignant cells.

Lactate dehydrogenase (LDH) tests are often used to screen for metastases, although many patients with metastases (even end-stage) have a normal LDH; extraordinarily high LDH often indicates metastatic spread of the disease to the liver.

It is common for patients diagnosed with melanoma to have chest X-rays and an LDH test, and in some cases CT, MRI, PET and/or PET/CT scans. Although controversial, sentinel lymph node biopsies and examination of the lymph nodes are also performed in patients to assess spread to the lymph nodes.

A diagnosis of melanoma is supported by the presence of the S-100 protein marker. Additionally, HMB-45 is a monoclonal antibody that reacts against an antigen present in melanocytic tumors such as melanomas. It is used in anatomic pathology as a marker for such tumors. The antibody was generated to an extract of melanoma. It reacts positively against melanocytic tumors, but not other tumors, thus demonstrating specificity and sensitivity.

The following are melanoma stages with 5 year survival rates. Stage 0: melanoma in situ (99.9% survival); Stage I/II: invasive melanoma (89-95% survival); Stage II: high risk melanoma (45-79% survival); Stage III: regional metastasis (24-70% survival); Stage IV: distant metastasis (7-19% survival).

Recent evidence suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology (Akbani et al., 2015 Cell (161), 1681-1696, incorporated herein by reference).

Melanoma Treatment

Treatment is typically removal by surgery. In those with slightly larger cancers, nearby lymph nodes may be tested for spread. Most people are cured after tumor excision if spread has not occurred. Excisional biopsies may remove the tumor, but further surgery is often necessary to reduce the risk of recurrence. Complete surgical excision with adequate surgical margins and assessment for the presence of detectable metastatic disease along with short- and long-term followup is standard. Often this is done by a wide local excision (WLE) with 1 to 2 cm margins.

For those in whom melanoma has spread, immunotherapy, biologic therapy, radiation therapy, or chemotherapy may improve survival. With treatment, the five-year survival rates in the United States is 98% among those with localized disease and 17% among those in whom spread has occurred. The likelihood that it will come back or spread depends on the melanoma thickness, how fast the cells are dividing, and whether or not the overlying skin has broken down.

Various chemotherapy agents, including temozolomide, dacarbazine (also termed DTIC), immunotherapy (with interleukin-2 (IL-2) or interferon (IFN)), as well as local perfusion, are used for treatment of melanoma. The overall success in metastatic melanoma is quite limited. Therapies for metastatic melanoma include biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor, trametinib.

Radiation therapy is often used after surgical resection for patients with locally or regionally advanced melanoma or for patients with unresectable distant metastases. Kilovoltage x-ray beams are often used for these treatments and have the property of the maximum radiation dose occurring close to the skin surface.

CTLA-4-Blockade

CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that, functioning as an immune checkpoint, downregulates immune responses. CTLA4 is constitutively expressed in regulatory T cells (Tregs), but only upregulated in conventional T cells after activation. CTLA4 acts as an “off” switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. Recent reports suggest that blocking CTLA4 (using antagonistic antibodies against CTLA such as ipilimumab (FDA approved for melanoma in 2011)) results in therapeutic benefit. CTLA4 blockade inhibits immune system tolerance to tumors and provides a useful immunotherapy strategy for patients with cancer. See, Grosso J. and Jure-Kunkel M. 2013, Cancer Immun., 13: 5, incorporated herein by reference.

Ipilimumab, a fully human monoclonal antibody specific to CTLA-4, improves overall survival in metastatic melanoma patients (Ji et al., 2012 Cancer Immunol Immunother, 61: 1019-1031, incorporated herein by reference). Indeed, monoclonal antibodies directed against CTLA4, such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting checkpoint activity; however, prior to the invention described herein, clinical predictors of response to these therapies were incompletely characterized (Van Allen, et al., 2015 Science, 350(6257): 207-211, incorporated herein by reference). See also, Snyder et al., 2014 The New England Journal of Medicine, 373(20): 1984, incorporated herein by reference.

World Health Organization Criteria

The WHO Criteria for evaluating the effectiveness of anti-cancer agents on tumor shrinkage, developed in the 1970s by the International Union Against Cancer and the World Health Organization, represented the first generally agreed specific criteria for the codification of tumor response evaluation. These criteria were first published in 1981 (Miller et al., 1981 Clin Cancer Res., 47(1): 207-14, incorporated herein by reference). WHO Criteria proposed >50% tumour shrinkage for a Partial Response and >25% tumour increase for Progressive Disease.

Response Evaluation Criteria in Solid Tumors (RECIST)

RECIST is a set of published rules that define when tumors in cancer patients improve (“respond”), stay the same (“stabilize”), or worsen (“progress”) during treatment (Eisenhauer et al., 2009 European Journal of Cancer, 45: 228-247, incorporated herein by reference). Only patients with measurably disease at baseline should be included in protocols where objective tumor response is the primary endpoint.

The response criteria for evaluation of target lesions are as follows:

-   -   Complete Response (CR): Disappearance of all target lesions.     -   Partial Response (PR): At least a 30% decrease in the sum of the         longest diameter (LD) of target lesions, taking as reference the         baseline sum LD.     -   Stable Disease (SD): Neither sufficient shrinkage to qualify for         PR nor sufficient increase to qualify for PD, taking as         reference the smallest sum LD since the treatment started.     -   Progressive Disease (PD): At least a 20% increase in the sum of         the LD of target lesions, taking as reference the smallest sum         LD recorded since the treatment started or the appearance of one         or more new lesions.     -   The response criteria for evaluation of non-target lesions are         as follows:     -   Complete Response (CR): Disappearance of all non-target lesions         and normalization of tumor marker level.     -   Incomplete Response/Stable Disease (SD): Persistence of one or         more non-target lesion(s) or/and maintenance of tumor marker         level above the normal limits.     -   Progressive Disease (PD): Appearance of one or more new lesions         and/or unequivocal progression of existing non-target lesions.

The response criteria for evaluation of best overall response are as follows. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the treatment started). In general, the patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

-   -   Patients with a global deterioration of health status requiring         discontinuation of treatment without objective evidence of         disease progression at that time should be classified as having         “symptomatic deterioration”. Every effort should be made to         document the objective progression even after discontinuation of         treatment.     -   In some circumstances, it may be difficult to distinguish         residual disease from normal tissue. When the evaluation of         complete response depends on this determination, it is         recommended that the residual lesion be investigated (fine         needle aspirate/biopsy) to confirm the complete response status.

Immune-Related Response Criteria

The immune-related response criteria (irRC) is a set of published rules that define when tumors in cancer patients improve (“respond”), stay the same (“stabilize”), or worsen (“progress”) during treatment, where the compound being evaluated is an immuno-oncology drug. The Immune-Related Response Criteria, first published in 2009 (Wolchok et al., 2009 Clin Cancer Res, 15(23):7412, incorporated herein by reference), arose out of observations that immuno-oncology drugs would fail in clinical trials that measured responses using the WHO or RECIST Criteria, because these criteria could not account for the time gap in many patients between initial treatment and the apparent action of the immune system to reduce the tumor burden. The key driver in the development of the irRC was the observation that, in studies of various cancer therapies derived from the immune system such as cytokines and monoclonal antibodies, the looked-for Complete and Partial Responses as well as Stable Disease only occurred after an increase in tumor burden that the conventional RECIST Criteria would have dubbed “Progressive Disease’. RECIST failed to take account of the delay between dosing and an observed anti-tumour T cell response, so that otherwise ‘successful’ drugs—that is, drugs which ultimately prolonged life—failed in clinical trials.

The irRC are based on the WHO Criteria; however, the measurement of tumor burden and the assessment of immune-related response have been modified as set forth below.

Measurement of Tumor Burden

In the irRC, tumor burden is measured by combining ‘index’ lesions with new lesions. Ordinarily, tumor burden would be measured with a limited number of ‘index’ lesions (that is, the largest identifiable lesions) at baseline, with new lesions identified at subsequent timepoints counting as ‘Progressive Disease’. In the irRC, by contrast, new lesions are a change in tumor burden. The irRC retained the bidirectional measurement of lesions that had originally been laid down in the WHO Criteria.

Assessment of Immune-Related Response

In the irRC, an immune-related Complete Response (irCR) is the disappearance of all lesions, measured or unmeasured, and no new lesions; an immune-related Partial Response (irPR) is a 50% drop in tumor burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a 25% increase in tumor burden from the lowest level recorded. Everything else is considered immune-related Stable Disease (irSD). Even if tumor burden is rising, the immune system is likely to “kick in” some months after first dosing and lead to an eventual decline in tumor burden for many patients. The 25% threshold accounts for this apparent delay.

The Cancer Genome Atlas (TCGA)

The Cancer Genome Atlas (TCGA) is a project to catalogue genetic mutations responsible for cancer, using genome sequencing and bioinformatics (Cancer Genome Atlas N. Genomic Classification of Cutaneous Melanoma. 2015 Cell, 161(7):1681-96, incorporated herein by reference). TCGA applies high-throughput genome analysis techniques to improve the ability to diagnose, treat, and prevent cancer through a better understanding of the genetic basis of this disease.

The project scheduled 500 patient samples, more than most genomics studies, and used different techniques to analyze the patient samples. Techniques include gene expression profiling, copy number variation profiling, SNP genotyping, genome wide DNA methylation profiling, microRNA profiling, and exon sequencing of at least 1,200 genes. TCGA is sequencing the entire genomes of some tumors, including at least 6,000 candidate genes and microRNA sequences. This targeted sequencing is being performed by all three sequencing centers using hybrid-capture technology. In phase II, TCGA is performing whole exon sequencing on 80% of the cases and whole genome sequencing on 80% of the cases used in the project.

Gene Expression Profiling

In general, methods of gene expression profiling can be divided into two large groups: methods based on hybridization analysis of polynucleotides, and methods based on sequencing of polynucleotides. Methods known in the art for the quantification of mRNA expression in a sample include northern blotting and in situ hybridization, RNAse protection assays, RNA-seq, and reverse transcription polymerase chain reaction (RT-PCR). Alternatively, antibodies are employed that recognize specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. Representative methods for sequencing-based gene expression analysis include Serial Analysis of Gene Expression (SAGE), and gene expression analysis by massively parallel signature sequencing (MPSS). For example, RT-PCR is used to compare mRNA levels in different sample populations, in normal and tumor tissues, with or without drug treatment, to characterize patterns of gene expression, to discriminate between closely related mRNAs, and/or to analyze RNA structure.

In some cases, a first step in gene expression profiling by RT-PCR is the reverse transcription of the RNA template into cDNA, followed by amplification in a PCR reaction. For example, extracted RNA is reverse-transcribed using a GeneAmp RNA PCR kit (Perkin Elmer, Calif., USA), following the manufacturer's instructions. The cDNA is then used as template in a subsequent PCR amplification and quantitative analysis using, for example, a TaqMan® (Life Technologies, Inc., Grand Island, N.Y.) assay.

Microarrays

Differential gene expression can also be identified, or confirmed using a microarray technique. In these methods, polynucleotide sequences of interest (including cDNAs and oligonucleotides) are plated, or arrayed, on a microchip substrate. The arrayed sequences are then hybridized with specific DNA probes from cells or tissues of interest. Just as in the RT-PCR method, the source of mRNA typically is total RNA isolated from human tumors or tumor cell lines and corresponding normal tissues or cell lines. Thus, RNA is isolated from a variety of primary tumors or tumor cell lines. If the source of mRNA is a primary tumor, mRNA is extracted from frozen or archived tissue samples.

In the microarray technique, PCR-amplified inserts of cDNA clones are applied to a substrate in a dense array. The microarrayed genes, immobilized on the microchip, are suitable for hybridization under stringent conditions.

In some cases, fluorescently labeled cDNA probes are generated through incorporation of fluorescent nucleotides by reverse transcription of RNA extracted from tissues of interest (e.g., melanoma tissue). Labeled cDNA probes applied to the chip hybridize with specificity to loci of DNA on the array. After washing to remove non-specifically bound probes, the chip is scanned by confocal laser microscopy or by another detection method, such as a charge-coupled device (CCD) camera. Quantification of hybridization of each arrayed element allows for assessment of corresponding mRNA abundance.

In some configurations, dual color fluorescence is used. With dual color fluorescence, separately labeled cDNA probes generated from two sources of RNA are hybridized pairwise to the array. The relative abundance of the transcripts from the two sources corresponding to each specified gene is thus determined simultaneously. In various configurations, the miniaturized scale of the hybridization can afford a convenient and rapid evaluation of the expression pattern for large numbers of genes. In various configurations, such methods can have sensitivity required to detect rare transcripts, which are expressed at fewer than 1000, fewer than 100, or fewer than 10 copies per cell. In various configurations, such methods can detect at least approximately two-fold differences in expression levels (Schena et al., Proc. Natl. Acad. Sci. USA 93(2): 106-149 (1996)). In various configurations, microarray analysis is performed by commercially available equipment, following manufacturer's protocols, such as by using the Affymetrix GenChip technology, or Incyte's microarray technology.

RNA-seq

RNA sequencing (RNA-seq), also called whole transcriptome shotgun sequencing (WTSS), uses next-generation sequencing (NGS) to reveal the presence and quantity of RNA in a biological sample at a given moment in time.

RNA-Seq is used to analyze the continually changing cellular transcriptome. See, e.g., Wang et al., 2009 Nat Rev Genet, 10(1): 57-63, incorporated herein by reference. Specifically, RNA-Seq facilitates the ability to look at alternative gene spliced transcripts, post-transcriptional modifications, gene fusion, mutations/SNPs and changes in gene expression. In addition to mRNA transcripts, RNA-Seq can look at different populations of RNA to include total RNA, small RNA, such as miRNA, tRNA, and ribosomal profiling. RNA-Seq can also be used to determine exon/intron boundaries and verify or amend previously annotated 5′ and 3′ gene boundaries.

Prior to RNA-Seq, gene expression studies were done with hybridization-based microarrays. Issues with microarrays include cross-hybridization artifacts, poor quantification of lowly and highly expressed genes, and needing to know the sequence of interest. Because of these technical issues, transcriptomics transitioned to sequencing-based methods. These progressed from Sanger sequencing of Expressed Sequence Tag libraries, to chemical tag-based methods (e.g., serial analysis of gene expression), and finally to the current technology, NGS of cDNA (notably RNA-Seq).

Gene Signature

As described here, a gene signature was defined herein, which distinguishes CTLA-4 response in melanoma patients. Also described herein is a gene signature which distinguishes response to a combination of CTLA-4 blockade and a TLR (or autophagy) agonist. Exemplary distinguishing genes are provided below.

An exemplary human MAGEA2 amino acid sequence is set forth below (SEQ ID NO: 1; GenBank Accession No: NP_001269434, Version 1, incorporated herein by reference):

   1 mpleqrsqhc kpeeglearg ealglvgaqa pateeqqtas ssstlvevtl gevpaadsps   61 pphspqgass fsttinytlw rqsdegssnq eeegprmfpd lesefqaais rkmvelvhfl  121 llkyrarepv tkaemlesvl rncqdffpvi fskaseylql vfgievvevv pishlyilvt  181 clglsydgll gdnqvmpktg lliivlaiia iegdcapeek iweelsmlev fegredsvfa  241 hprkllmqdl vqenyleyrq vpgsdpacye flwgpralie tsyvkvlhht lkiggephis  301 ypplheralr egee

An exemplary human MAGEA2 nucleic acid sequence is set forth below (SEQ ID NO: 2; GenBank Accession No: NM_001282505, Version 1, incorporated herein by reference):

   1 ttgcgcattg gaggtcagag gacagcgaga ttctcgccct gagcaacggc ctgacgtcgg   61 cggagggaag caggcgcagg ctccgtgagg aggcaaggcc tgtgggtctt cattgcccag  121 ctcctgcccg cactcctgcc tgctgccctg accagagtca tcatgcctct tgagcagagg  181 agtcagcact gcaagcctga agaaggcctt gaggcccgag gagaggccct gggcctggtg  241 ggtgcgcagg ctcctgctac tgaggagcag cagaccgctt cttcctcttc tactctagtg  301 gaagttaccc tgggggaggt gcctgctgcc gactcaccga gtcctcccca cagtcctcag  361 ggagcctcca gcttctcgac taccatcaac tacactcttt ggagacaatc cgatgagggc  421 tccagcaacc aagaagagga ggggccaaga atgtttcccg acctggagtc cgagttccaa  481 gcagcaatca gtaggaagat ggttgagttg gttcattttc tgctcctcaa gtatcgagcc  541 agggagccgg tcacaaaggc agaaatgctg gagagtgtcc tcagaaattg ccaggacttc  601 tttcccgtga tcttcagcaa agcctccgag tacttgcagc tggtctttgg catcgaggtg  661 gtggaagtgg tccccatcag ccacttgtac atccttgtca cctgcctggg cctctcctac  721 gatggcctgc tgggcgacaa tcaggtcatg cccaagacag gcctcctgat aatcgtcctg  781 gccataatcg caatagaggg cgactgtgcc cctgaggaga aaatctggga ggagctgagt  841 atgttggagg tgtttgaggg gagggaggac agtgtcttcg cacatcccag gaagctgctc  901 atgcaagatc tggtgcagga aaactacctg gagtaccggc aggtgcccgg cagtgatcct  961 gcatgctacg agttcctgtg gggtccaagg gccctcattg aaaccagcta tgtgaaagtc 1021 ctgcaccata cactaaagat cggtggagaa cctcacattt cctacccacc cctgcatgaa 1081 cgggctttga gagagggaga agagtgagtc tcagcacatg ttgcagccag ggccagtggg 1141 agggggtctg ggccagtgca ccttccaggg ccccatccat tagcttccac tgcctcgtgt 1201 gatatgaggc ccattcctgc ctctttgaag agagcagtca gcattcttag cagtgagttt 1261 ctgttctgtt ggatgacttt gagatttatc tttgtttcct gttggaattg ttcaaatgtt 1321 ccttttaaca aatggttgga tgaacttcag catccaagtt tatgaatgac agtagtcaca 1381 catagtgctg tttatatagt ttaggggtaa gagtcctgtt ttttattcag attgggaaat 1441 ccattccatt ttgtgagttg tcacataata acagcagtgg aatatgtatt tgcctatatt 1501 gtgaacgaat tagcagtaaa atacatgata caaggaactc aaaagatagt taattcttgc 1561 cttatacctc agtctattat gtaaaattaa aaatatgtgt atgtttttgc ttctttgaga 1621 atgcaaaaga aattaaatct gaataaataa ttcttcctgt tcaaaaaaaa aaaaaaaaaa

An exemplary human MAGEA3 amino acid sequence is set forth below (SEQ ID NO: 3; GenBank Accession No: CAG46566.1, Version 1, incorporated herein by reference):

  1 mpleqrsqhc kpeeglearg ealglvgaqa pateeqeaas ssstivevtl gevpaaespd  61 ppqspqgass lpttmnyplw sqsyedssnq eeegpstfpd lesefqaals rkvaelvhfl 121 llkyrarepv tkaemlgsvv gnwqyffpvi fskassslql vfgielmevd pighlyifat 181 clglsydgll gdnqimpkag lliivlaiia regdcapeek iweelsvlev fegredsilg 241 dpkklltqhf vqenyleyrq vpgsdpacye flwgpralve tsyvkvlhhm vkisggphis 301 ypplhewvlr egee

An exemplary human MAGEA3 nucleic acid sequence is set forth below (SEQ ID NO: 4; GenBank Accession No: NM_005362.3, Version 3, incorporated herein by reference):

   1 gagattctcg ccctgagcaa cgagcgacgg cctgacgtcg gcggagggaa gccggcccag   61 gctcggtgag gaggcaaggt tctgagggga caggctgacc tggaggacca gaggcccccg  121 gaggagcact gaaggagaag atctgccagt gggtctccat tgcccagctc ctgcccacac  181 tcccgcctgt tgccctgacc agagtcatca tgcctcttga gcagaggagt cagcactgca  241 agcctgaaga aggccttgag gcccgaggag aggccctggg cctggtgggt gcgcaggctc  301 ctgctactga ggagcaggag gctgcctcct cctcttctac tctagttgaa gtcaccctgg  361 gggaggtgcc tgctgccgag tcaccagatc ctccccagag tcctcaggga gcctccagcc  421 tccccactac catgaactac cctctctgga gccaatccta tgaggactcc agcaaccaag  481 aagaggaggg gccaagcacc ttccctgacc tggagtccga gttccaagca gcactcagta  541 ggaaggtggc cgagttggtt cattttctgc tcctcaagta tcgagccagg gagccggtca  601 caaaggcaga aatgctgggg agtgtcgtcg gaaattggca gtatttcttt cctgtgatct  661 tcagcaaagc ttccagttcc ttgcagctgg tctttggcat cgagctgatg gaagtggacc  721 ccatcggcca cttgtacatc tttgccacct gcctgggcct ctcctacgat ggcctgctgg  781 gtgacaatca gatcatgccc aaggcaggcc tcctgataat cgtcctggcc ataatcgcaa  841 gagagggcga ctgtgcccct gaggagaaaa tctgggagga gctgagtgtg ttagaggtgt  901 ttgaggggag ggaagacagt atcttggggg atcccaagaa gctgctcacc caacatttcg  961 tgcaggaaaa ctacctggag taccggcagg tccccggcag tgatcctgca tgttatgaat 1021 tcctgtgggg tccaagggcc ctcgttgaaa ccagctatgt gaaagtcctg caccatatgg 1081 taaagatcag tggaggacct cacatttcct acccacccct gcatgagtgg gttttgagag 1141 agggggaaga gtgagtctga gcacgagttg cagccagggc cagtgggagg gggtctgggc 1201 cagtgcacct tccggggccg catcccttag tttccactgc ctcctgtgac gtgaggccca 1261 ttcttcactc tttgaagcga gcagtcagca ttcttagtag tgggtttctg ttctgttgga 1321 tgactttgag attattcttt gtttcctgtt ggagttgttc aaatgttcct tttaacggat 1381 ggttgaatga gcgtcagcat ccaggtttat gaatgacagt agtcacacat agtgctgttt 1441 atatagttta ggagtaagag tcttgttttt tactcaaatt gggaaatcca ttccattttg 1501 tgaattgtga cataataata gcagtggtaa aagtatttgc ttaaaattgt gagcgaatta 1561 gcaataacat acatgagata actcaagaaa tcaaaagata gttgattctt gccttgtacc 1621 tcaatctatt ctgtaaaatt aaacaaatat gcaaaccagg atttccttga cttctttgag 1681 aatgcaagcg aaattaaatc tgaataaata attcttcctc ttcaaaaaaa aaaaaaaaaa 1741 aaaaaaaaaa aaa

An exemplary human MAGEA6 amino acid sequence is set forth below (SEQ ID NO: 5; GenBank Accession No: CAG46567.1, Version 1, incorporated herein by reference):

  1 mpleqrsqhc kpeeglearg ealglvgaqa pateeqeaas ssstlvevtl gevpaaespd  61 ppgspqgass lpttmnyplw sqsyedssnq eeegpstfpd lesefqaals rkvaklvhfl 121 llkyrarepv tkaemlgsvv gnwqyffpvi fskasdslql vfgielmevd pighvyifat 181 clglsydgll gdnqimpktg fliiilaiia kegdcapeek iweelsvlev fegredsifg 241 dpkklltqyf vqenyleyrq vpgsdpacye flwgpralie tsyvkvlhhm vkisggpris 301 ypllhewafr egee

An exemplary human MAGEA6 nucleic acid sequence is set forth below (SEQ ID NO: 6; GenBank Accession No: NM_005362.3, Version 3, incorporated herein by reference):

   1 gagattctcg ccctgagcaa cgagcgacgg cctgacgtcg gcggagggaa gccggcccag   61 gctcggtgag gaggcaaggt tctgagggga caggctgacc tggaggacca gaggcccccg  121 gaggagcact gaaggagaag atctgccagt gggtctccat tgcccagctc ctgcccacac  181 tcccgcctgt tgccctgacc agagtcatca tgcctcttga gcagaggagt cagcactgca  241 agcctgaaga aggccttgag gcccgaggag aggccctggg cctggtgggt gcgcaggctc  301 ctgctactga ggagcaggag gctgcctcct cctcttctac tctagttgaa gtcaccctgg  361 gggaggtgcc tgctgccgag tcaccagatc ctccccagag tcctcaggga gcctccagcc  421 tccccactac catgaactac cctctctgga gccaatccta tgaggactcc agcaaccaag  481 aagaggaggg gccaagcacc ttccctgacc tggagtccga gttccaagca gcactcagta  541 ggaaggtggc cgagttggtt cattttctgc tcctcaagta tcgagccagg gagccggtca  601 caaaggcaga aatgctgggg agtgtcgtcg gaaattggca gtatttcttt cctgtgatct  661 tcagcaaagc ttccagttcc ttgcagctgg tctttggcat cgagctgatg gaagtggacc  721 ccatcggcca cttgtacatc tttgccacct gcctgggcct ctcctacgat ggcctgctgg  781 gtgacaatca gatcatgccc aaggcaggcc tcctgataat cgtcctggcc ataatcgcaa  841 gagagggcga ctgtgcccct gaggagaaaa tctgggagga gctgagtgtg ttagaggtgt  901 ttgaggggag ggaagacagt atcttggggg atcccaagaa gctgctcacc caacatttcg  961 tgcaggaaaa ctacctggag taccggcagg tccccggcag tgatcctgca tgttatgaat 1021 tcctgtgggg tccaagggcc ctcgttgaaa ccagctatgt gaaagtcctg caccatatgg 1081 taaagatcag tggaggacct cacatttcct acccacccct gcatgagtgg gttttgagag 1141 agggggaaga gtgagtctga gcacgagttg cagccagggc cagtgggagg gggtctgggc 1201 cagtgcacct tccggggccg catcccttag tttccactgc ctcctgtgac gtgaggccca 1261 ttcttcactc tttgaagcga gcagtcagca ttcttagtag tgggtttctg ttctgttgga 1321 tgactttgag attattcttt gtttcctgtt ggagttgttc aaatgttcct tttaacggat 1381 ggttgaatga gcgtcagcat ccaggtttat gaatgacagt agtcacacat agtgctgttt 1441 atatagttta ggagtaagag tcttgttttt tactcaaatt gggaaatcca ttccattttg 1501 tgaattgtga cataataata gcagtggtaa aagtatttgc ttaaaattgt gagcgaatta 1561 gcaataacat acatgagata actcaagaaa tcaaaagata gttgattctt gccttgtacc 1621 tcaatctatt ctgtaaaatt aaacaaatat gcaaaccagg atttccttga cttctttgag 1681 aatgcaagcg aaattaaatc tgaataaata attcttcctc ttcaaaaaaa aaaaaaaaaa 1741 aaaaaaaaaa aaa

An exemplary human MAGEA12 amino acid sequence is set forth below (SEQ ID NO: 7; GenBank Accession No: EAW99432.1, Version 1, incorporated herein by reference):

  1 mpleqrsqhc kpeegleaqg ealglvgaqa pateeqetas ssstlvevtl revpaaesps  61 pphspqgast lpttinytlw sqsdegssne eqegpstfpd letsfqvals rkmaelvhfl 121 llkyrarepf tkaemlgsvi rnfqdffpvi fskaseylql vfgievvevv righlyilvt 181 clglsydgll gdnqivpktg lliivlaiia kegdcapeek iweelsvlea sdgredsvfa 241 hprklltqdl vqenyleyrq vpgsdpacye flwgpralve tsyvkvlhhl lkisggphis 301 ypplhewafr egee

An exemplary human MAGEA12 nucleic acid sequence is set forth below (SEQ ID NO: 8; GenBank Accession No: NM_001166386.3, Version 3, incorporated herein by reference):

   1 aagatgccga gggaggactg aggcgggcct caccccagac agagggcccc caataatcca   61 gcgctgcctc tgctgccggg cctggaccac cctgcagggg aagacttctc aggctgagtc  121 gccaccacct caccccgcca ccccccgccg ctttaaccgc agggaactct ggtatctcag  181 ggagttgagg accttttctt cagagggtga ctcaggtcaa cacaggggcc cccatgtagt  241 cgacagacac agtggtccta agatctacca agcatccagg ttctgaggag acaggccccg  301 gagcagcact agctcctgcc cacactccta cctgctgccc tgaccagagt catcatgcca  361 cttgagcaga ggagtcagca ctgcaagcct gaggaaggcc ttgaggccca aggagaggcc  421 ctgggcttgg tgggtgcgca ggctcctgct actgaggagc aggagactgc ctcctcctcc  481 tctactctag tggaagtcac cctgcgggag gtgcctgctg ccgagtcacc aagtcctccc  541 cacagtcctc agggagcctc caccctcccc actaccatca actatactct ctggagtcaa  601 tccgatgagg gctccagcaa cgaagaacag gaagggccaa gcacctttcc tgacctggag  661 acgagcttcc aagtagcact cagtaggaag atggctgagt tggttcattt tctgctcctc  721 aagtatcgag ccagggagcc attcacaaag gcagaaatgc tggggagtgt catcagaaat  781 ttccaggact tctttcctgt gatcttcagc aaagcctccg agtacttgca gctggtcttt  841 ggcatcgagg tggtggaagt ggtccgcatc ggccacttgt acatccttgt cacctgcctg  901 ggcctctcct acgatggcct gctgggcgac aatcagatcg tgcccaagac aggcctcctg  961 ataatcgtcc tggccataat cgcaaaagag ggcgactgtg cccctgagga gaaaatctgg 1021 gaggagctga gtgtgttgga ggcatctgat gggagggagg acagtgtctt tgcgcatccc 1081 aggaagctgc tcacccaaga tttggtgcag gaaaactacc tggagtaccg gcaggtcccc 1141 ggcagtgatc ctgcatgcta cgagttcctg tggggtccaa gggccctcgt tgaaaccagc 1201 tatgtgaaag tcctgcacca tttgctaaag atcagtggag gacctcacat ttcctaccca 1261 cccctgcatg aatgggcttt tagagagggg gaagagtgag tctgagcacg agttgcagcc 1321 agggccagtg ggagggggtc tgggccagtg caccttccaa ggccccatcc attagtttcc 1381 actgcctcgt gtgacatgag gcccattctt cactctttga agagagcagt cagtattgtt 1441 agtagtgagt ttctgttcta ttggatgact ttgagattta tctttgtttc ctgttggaat 1501 tgttcaaatg ttccttttaa cggatggttg aatgaacttc agcatccaag tttatgaatg 1561 acagtagtca cacatagtgc tgtttatata gtttaggagt aagagtgttg ttttttattc 1621 agattgggaa atccattcca ttttgtgaat tgtgacaaat aacagcagtg gaaaaagtat 1681 gtgcttagaa ttgtgaaaga attagcagta aaatacatga gataaagacc tcaagaagtt 1741 aaaagatact taattcttgc cttatacctc actctattct gtaaatttga aaaaaaagca 1801 tggatacctg gatatccttg gcttctttga gaatttaaga gaaattaaat ctgaataaat 1861 aa

An exemplary human CSAG1 amino acid sequence is set forth below (SEQ ID NO: 9; GenBank Accession No: AAH59947.1, Version 1, incorporated herein by reference):

 1 msattacwpa ftvlgeargd qvdwsrlyrd tglvkmsrkp rasspfsnnh pstpkrfprq 61 prrekgpvke vpgtkgsp

An exemplary human CSAG1 nucleic acid sequence is set forth below (SEQ ID NO: 10; GenBank Accession No: BC059947.1, Version 1, incorporated herein by reference):

  1 ctggattctt cctggatggg gatccagatg gaggtggagg gttgatttgg gaagcagagc  61 acagcagccc aaatttgctt gtaatgtcgg cgactacagc ctgctggcct gccttcactg 121 tcctggggga agctcgggga gaccaggtgg actggagtag actgtacaga gacactggtc 181 tggtgaagat gtccaggaaa ccacgagcct ccagcccatt ttccaacaac cacccatcaa 241 caccaaagag gttcccaaga caacccagaa gggaaaaggg acccgtcaag gaagttccag 301 gaacaaaagg ctctccctaa aagaccaccg cttcaaaaaa acctgaggaa tggagtgggc 361 caacactatc cagccactct gaccagccga acgaggaact caatcaaaat gcgccatagc 421 aggaccacaa gggcaaggag accaccgcct tctccagtgc ttccttgggc agccagtaat 481 tcccaggcaa ggccagagac ttcaagtcta tctgaaaagt ctccagaagt ctaaccccag 541 ataaatagcc aacagggtgt agagtacgtt ttacacccca aagggtatgc cccatggtga 601 tggaaataaa atgaacatgt tgtaaaaaaa aaaaaaaaaa aaa

An exemplary human CSAG2 amino acid sequence is set forth below (SEQ ID NO: 11; GenBank Accession No: EAW99427.1, Version 1, incorporated herein by reference):

  1 mwmgliqlve gvkrkdqgfl ekefyhktni kmrceflacw paftvlgeaw rdqvdwsrll  61 rdaglvkmsr kprassplsn nhpptpkrrg sgrhpinpgp ealskfprqp grekgpikev 121 pgtkgsp

An exemplary human CSAG2 nucleic acid sequence is set forth below (SEQ ID NO: 12; GenBank Accession No: AJ844639.1, Version 1, incorporated herein by reference):

  1 agttccagga acaaaaggct ctccctaaaa gaccgccgct tcaaaaaaac ctgaggaatg  61 gagtgggcca acactatcca gccactctga ccagccgaac gaggaactca atcaaaatga 121 gccatagcgg gaccacaagg gcaaggagac caccaccttc tccagtctct cttcggacag 181 ccagtaattc ccgggcaagg ccagagactt caa

An exemplary human CSAG3 amino acid sequence is set forth below (SEQ ID NO: 13; GenBank Accession No: AAI19736.1, Version 1, incorporated herein by reference):

 1 mwmgliqlve gvkrkdqgfl ekefyhktni kmrceflacw paftvlgeaw rdqvdwsrll 61 rdaglvkmsr kprassplsn nhpptpkrfp rqpgrekgpi kevpgtkgsp

An exemplary human CSAG3 nucleic acid sequence is set forth below (SEQ ID NO: 14; GenBank Accession No: NM_001129826.2, Version 2, incorporated herein by reference):

  1 gtgcaatggc tagtactatg tgtcaacttg tctaggctat actgctcagc tgtgtggtca  61 aacagtagtc tagatgttgc tgtgaaggta ttttgtagat gtgatcaaca tttacaatca 121 gttgatttta agtaaagcag tttaacttcc ataatgtgga tgggcctcat ccaattagtt 181 gaaggtgtta agagaaaaga ccaaggtttc ctggaaaagg aattctacca caagactaac 241 ataaaaatgc gctgtgagtt tctagcctgc tggcctgcct tcactgtcct gggggaggct 301 tggagagacc aggtggactg gagtagactg ttgagagacg ctggtctggt gaagatgtcc 361 aggaaaccac gagcctccag cccattgtcc aacaaccacc caccaacacc aaagaggcga 421 ggaagtggaa ggcatcctct caaccctggc ccagaagccc tatcaaagtt cccaagacaa 481 cccggaaggg aaaagggacc catcaaggaa gttccaggaa caaaaggctc tccctaaaag 541 accgccgctt caaaaaaacc tgaggaatgg agtgggccaa cactatccag ccactctgac 601 cagccgaacg aggaactcaa tcaaaatgag ccatagcggg accacaaggg caaggagacc 661 accaccttct ccagtctctc ttcggacagc cagtaattcc cgggcaaggc cagagacttc 721 aagtctatct gaaaagtctc cagaggtcta accccagata aatagccaac agggtgtaga 781 gtacatttta caccccaaag agtgtgcccc atggtgatga aaataaagtg aacatgttgc 841 aaaatga

An exemplary human PSG1 amino acid sequence is set forth below (SEQ ID NO: 15; GenBank Accession No: AAH58285.1, Version 1, incorporated herein by reference):

  1 mgtlsappct qrikwkglll tasllnfwnl pttaqvtiea eptkvsegkd vlllvhnlpq  61 nltgyiwykg qmrdlyhyit syvvdgeiii ygpaysgret aysnaslliq nvtredagsy 121 tlhiikgddg trgvtgrftf tlhletpkps isssnlnpre tmeaysltcd petpdasylw 181 wmngqslpmt hslklsetnr tlfllgvtky tagpyeceir npvsasrsdp vtlnllpklp 241 kpyitinnln prenkdvinf tcepksenyt yiwwlngqsl pvsprvkrpi enrililpsv 301 trnetgpyqc eirdryggir sdpvtlnvly gpdlpriyps ftyyrsgevl ylscsadsnp 361 paqyswtine kfqlpgqklf irhittkhsg lyvcsvrnsa tgkessksmt vevsdwtvp

An exemplary human PSG1 nucleic acid sequence is set forth below (SEQ ID NO: 16; GenBank Accession No: M93704.1, Version 1, incorporated herein by reference):

  1 cgaagctgcc caagccctac atcaccatca acaacttaaa ccccagggag aataaggatg  61 tcttaaactt cacctgtgaa cctaagagtg agaactacac ctacatttcg tggctaaatg 121 gtcagagcct cccggtcagt cccagggtaa agcgacccat tgaaaacagg atcctcattc 181 tacccagtgt cacgagaaat gaaacaggac cctatcaatg tgaaatacgg gaccgatatg 241 gtggcatccg cagtgaccca gtcaccctga atgtcctct

An exemplary human PSG2 amino acid sequence is set forth below (SEQ ID NO: 17; GenBank Accession No: AAH22316.1, Version 1, incorporated herein by reference):

  1 mgplsappct ehikwkglll tasllnfwnl pttaqvtiea qppkvsegkd vlllvhnlpq  61 nltgyiwykg qirdlyhyit syvvdgqiii ygpaysgret aysnaslliq nvtredagsy 121 tlhiikrgdg trgvtgyftf tlyletpkps isssnlnpre ametviltcd petpdtsyqw 181 wmnggslpmt hrfqlsetnr tlflfgvtky tagpyeceir nsgsasrsdp vtlnllhgpd 241 lprihpsytn yrsgdnlyls cfansnppaq yswtingkfq gsgqnlfipq ittkhsglyv 301 csvrnsatge esstsltvkv sastrigllp llnpt

An exemplary human PSG2 nucleic acid sequence is set forth below (SEQ ID NO: 18; GenBank Accession No: NM_031246.3, Version 3, incorporated herein by reference):

   1 gacagagagg tgtcctgggc ctgaccccac ccatgagcct gggaattgct gctgccccag   61 gaagaggctc agtgcagaag gaggaaggac agcacagctg acagccgtgc tcaggaagtt  121 tctggatcct aggctcatct ccacagagga gaacacacag gcagcagaga ccatggggcc  181 cctctcagcc cctccctgca cagagcacat caaatggaag gggctcctgg tcacagcatc  241 acttttaaac ttctggaacc tgcccaccac tgcccaagtc acgattgaag cccagccacc  301 aaaagtttcc gaggggaagg atgttcttct acttgtccac aatttgcccc agaatcttac  361 tggctacatc tggtacaaag ggcaaatcag ggacctctac cattacatta catcatatgt  421 agtagacggt caaataatta tatatgggcc tgcatatagt ggacgagaaa cagcatattc  481 caatgcatcc ctgctgatcc agaatgtcac ccgggaggac gcaggatcct acaccttaca  541 catcataaag cgaggtgatg ggactagagg agtaactgga tatttcacct tcaccttata  601 cctggagact cccaagccct ccatctccag cagcaactta aaccccaggg aggccatgga  661 aactgtgatc ttaacctgtg atcctgagac tccggacaca agctaccagt ggtggatgaa  721 tggtcagagc ctccctatga ctcataggtt tcagctgtcc gaaaccaaca ggaccctctt  781 tctatttggt gtcacaaagt atactgcagg accctatgaa tgtgaaatac ggaactcagg  841 gagtgccagc cgcagtgacc cagtcaccct gaatctcctc catggtccag acctccccag  901 aattcaccct tcatacacca attaccgttc aggagataac ctctacttgt cttgcttcgc  961 gaactctaac ccaccggcac agtattcttg gacaattaat gggaagtttc agcaatcagg 1021 acaaaatctg tttatccccc aaattactac aaagcatagc gggctctatg tttgctctgt 1081 tcgtaactca gccactggcg aggaaagctc cacatcgttg acagtcaaag tctctgcttc 1141 tacaagaata ggacttcttc ctctccttaa tccaacatag cagctgtgat gtcatttctg 1201 tatttcagga agactggcag gagatttatg gaaaggtctc ttacaaggac tcttgaatac 1261 aagctcctga taacttcaag atcataccac tggactaaga actttcaaaa ttttaatgaa 1321 caggctgata ccttcatgaa attcaagaca aagaagaaaa atactcaatg ttattggact 1381 aaataatcaa aaggataatg atttcataat tttctatttg aaaatgtgct gattcttgga 1441 atgtttcatt ctccagattt atgaacattt tttcttgagc aattggtaaa gtatactttt 1501 gtaaacaaaa attgaaacat ttccttttgc tctctatctg agtgccccag aattgggaat 1561 ctattcatga gtattcatat gtttatggta ataaagctat ttgcacaagt tc

An exemplary human PSG4 amino acid sequence is set forth below (SEQ ID NO: 19; GenBank Accession No: AAH08405.1, Version 1, incorporated herein by reference):

  1 mgtlsappct qrikwkglll tasllnfwnl pttaqvtiea eptkvsegkd vlllvhnlpq  61 nltgyiwykg qmrdlyhyit syvvdgeiii ygpayggret aysnaslliq nvtredagsy 121 tlhiikgddg trgvtgrftf tlhletpkps isssnlnpre tmeaysltcd petpdasylw 181 wmngqslpmt hslklsetnr tlfllgvtky tagpyeceir npvsasrsdp vtlnllpkls 241 kpyitinnln prenkdvltf tcepksenyt yiwwlngqsl pvsprvkrpi enrililpnv 301 trnetgpyqc eirdryggir sdpvtlnvly gpdlpsiyps ftyyrsgenl ylscfaesnp 361 raqyswting kfqlsgqkls ipqittkhsg lyacsvrnsa tgkessksit vkvsdwilp

An exemplary human PSG4 nucleic acid sequence is set forth below (SEQ ID NO: 20; GenBank Accession No: M94891.1, Version 1, incorporated herein by reference):

   1 ggacagcaca gctgacagcc gtactcagga agcttctgga tcctaggctt atctccacag   61 aggagaacac acaagcagca gagaccatgg ggcccctctc agcccctccc tgcacacacc  121 tcatcacttg gaaggggctc ctgctcacag catcactttt aaacttctgg aatccgccca  181 caactgccca agtcacgatt gaagcccagc cacccaaagt ttctgagggg aaggatgttc  241 ttctacttgt ccacaatttg ccccagaatc ttgctggcta catttggtac aaagggcaaa  301 tgacatacgt ctaccattac attacatcat atgtagtaga cggtcaaaga attatatatg  361 ggcctgcata cagtggaaga gaaagagtat attccaatgc atccctgctg atccagaatg  421 tcacgcagga ggatgcagga tcctacacct tacacatcat aaagcgacgc gatgggactg  481 gaggagtaac tggacatttc accttcacct tacacctgga gactcccaag ccctccatct  541 ccagcagcaa cttaaatccc agggaggcca tggaggctgt gatcttaacc tgtgatcctg  601 cgactccagc cgcaagctac cagtggtgga tgaatggtca gagcctccct atgactcaca  661 ggttgcagct gtccaaaacc aacaggaccc tctttatatt tggtgtcaca aagtatattg  721 caggacccta tgaatgtgaa atacggaacc cagtgagtgc cagccgcagt gacccagtca  781 ccctgaatct cctcccaaag ctgtccaagc cctacatcac aatcaacaac ttaaacccca  841 gagagaataa ggatgtctta accttcacct gtgaacctaa gagtgagaac tacacctaca  901 tttggtggct aaatggtcag agcctccctg tcagtcccag ggtaaagcga cccattgaaa  961 acaggatcct cattctaccc aatgtcacga gaaatgaaac aggaccttat caatgtgaaa 1021 tacgggaccg atatggtggc atccgcagtg acccagtcac cctgaatgtc ctctatggtc 1081 cagacctccc cagcatttac ccttcattca cctattaccg ttcaggagaa aacctctact 1141 tgtcctgctt cgccgagtct aacccacggg cacaatattc ttggacaatt aatgggaagt 1201 ttcagctatc aggacaaaag ctctctatcc cccaaataac tacaaagcat agtgggctct 1261 atgcttgctc tgttcgtaac tcagccactg gcaaggaaag ctccaaatcc atcacagtca 1321 aagtctctga ctggatatta ccctgaattc tactagttcc tccaattcca ttttctccca 1381 tggaatcacg aagagcaaga cccactctgt tccagaagcc ctataagctg gaggtggaca 1441 actcgatgta aatttcatgg gaaaaccctt gtacctgaca tgtgagccac tcagaactca 1501 ccaaaatgtt cgacaccata acaacagcta ctcaaactgt aaaccaggat aagaagttga 1561 tgacttcaca ctgtggacag tttttccaaa gatgtcagaa caagactccc catcatgata 1621 aggctcccac ccctcttaac tgtccttgct catgcctgcc tctttcactt ggcaggataa 1681 tgcagtcatt agaatttcac atgtagtagc ttctgagggt aacaacagag tgtcagatat 1741 gtcatctcaa cctcaaactt ttacgtaaca tctcagggga aatgtggctc tctccatctt 1801 gcatacaggg ctcccaatag aaatgaacac agagatattg cctgtgtgtt tgcagagaag 1861 atggtttcta taaagagtag gaaagctgaa attatagtag agtctccttt aaatgcacat 1921 tgtgtggatg gctctcacca tttcctaaga gatacagtgt aaaacgtgac agtaatactg 1981 attctagcag aataaaacat gtaccacatt tgctaaaaaa aaaaaaaaaa aaaaaaaaaa 2041 aaa

An exemplary human PSG5 amino acid sequence is set forth below (SEQ ID NO: 21; GenBank Accession No: AAH12607.1, Version 1, incorporated herein by reference):

  1 mgplsappct qhitwkgvll tasllnfwnl pitaqvtiea lppkvsegkd vlllvhnlpq  61 nlagyiwykg qlmdlyhyit syvvdgqini ygpaytgret vysnaslliq nvtredagsy 121 tlhiikrgdr trgvtgyftf nlylklpkpy itinnskpre nkdvlaftce pksenytyiw 181 wlngqslpvs prvkqpienr ililpsvtrn etgpyeceir drdggmhsdp vtlnvlygpd 241 lpsiypsfty yrsgenlyls cfaesnppae yfwtingkfq qsgqklsipq ittkhrglyt 301 csvrnsatgk essksmtvev sapsgigrlp llnpi

An exemplary human PSG5 nucleic acid sequence is set forth below (SEQ ID NO: 22; GenBank Accession No: BC012607.1, Version 1, incorporated herein by reference):

   1 ggggaaggag gaaggacagc acagcctaca gccgtgctca ggaagtttct ggatcctagg   61 ctcagctcca cagaggagaa cacgcaggcg cagagaccat ggggcccctc tcagcccctc  121 cctgcacaca gcacatcacc tggaaggggg tcctgctcac agcatcactt ttaaacttct  181 ggaacctgcc tatcactgct caagtcacga ttgaagccct gccacccaaa gtttccgagg  241 ggaaggatgt tcttctactt gtccacaatt tgcctcagaa tcttgctggc tacatctggt  301 acaaaggaca actgatggac ctctaccatt acattacatc atatgtagta gacggtcaaa  361 taaatatata tgggcctgca tacactggac gagaaacagt atattccaat gcatccctgc  421 tgatccagaa tgtcacccgg gaagacgcag gatcctatac cttacacatc ataaagcgag  481 gtgataggac tagaggagta actggatatt tcaccttcaa cttatacctg aagctgccca  541 agccctacat caccatcaac aactcaaaac ccagggagaa taaggatgtc ttagccttca  601 cctgtgaacc taagagtgag aactacacct acatttggtg gctaaatggt cagagcctcc  661 cggtcagtcc cagggtaaag caacccattg aaaacaggat cctcattcta cccagtgtca  721 cgagaaatga aacaggaccc tatgaatgtg aaatacggga ccgagatggt ggcatgcaca  781 gtgacccagt caccctgaat gtcctctatg gtccagacct ccccagcatt tacccttcat  841 tcacctatta ccgttcagga gaaaacctct acttgtcctg cttcgcggaa tctaacccac  901 cggcagagta tttttggaca attaatggga agtttcagca atcaggacaa aagctctcta  961 tcccccaaat tactacaaag catagagggc tctatacttg ctctgttcgt aactcagcca 1021 ctggcaagga aagctccaaa tccatgacag tcgaagtctc tgctccttca ggaataggac 1081 gtcttcctct ccttaatcca atatagcagc cgtgaagtca tttctgtatt tcaggaagac 1141 tggcagacag ttgctttgat tcttcctcaa actacttaca atcacctaca gtccaaaatt 1201 gctttttctt caaggagatt tatggaaaag actctgacaa ggactcttga atacaagttc 1261 ctgataactt caagatcata ccactggact aagaactttc aaaattttaa tgaacaggct 1321 gataccttca tgaaattcta gacaaagaag aaaaaaactc catgttattg gactaaataa 1381 tcaaaagcat aatgttttca taattttcta tttgaaaatg tgctgattct ttgaatgttt 1441 tattctccag atttatgaac tttttttctt gagcaattgg taaagtatac ttttgtaaac 1501 aaaaattgaa acatttgctt ttactctcta tctgagtgcc ccagaattgg gaaactattc 1561 atgagtattc atatgtttat ggtaataaag ttatctgcac aagttcaaaa aaaaaaaaaa 1621 aaaaaaaaaa aaaaaa

An exemplary human PSG6 amino acid sequence is set forth below (SEQ ID NO: 23; GenBank Accession No: AAC25619.1, Version 1, incorporated herein by reference):

  1 mgplsappct qhitwkglll tasllnfwnl pttaqviiea kppkvsegkd vlllvhnlpq  61 nltgyiwykg qmtdlyhyit syvvhgqiiy gpaysgretv ysnaslliqn vtqedagsyt 121 lhiikrgdgt ggvtgyftvt lysetpkpsi sssnlnprev meavrlicdp etpdasylwl 181 lngqnlpmth rlqlsktnrt lylfgvtkyi agpyeceirn pvsasrsdpv tlnllpklpm 241 pyitinnlnp rekkdvlaft cepksrnyty iwwlngqslp vsprvkrpie nrililpsvt 301 rnetgpyqce irdryggirs npvtlnvlyg pdlpriypsf tyyrsgenld lscfadsnpp 361 aeyswtingk fqlsgqklfi pqittnhsgl yacsvrnsat gkeisksmiv kvsetaspqv 421 tyagpntwfq eilll

An exemplary human PSG6 nucleic acid sequence is set forth below (SEQ ID NO: 24; GenBank Accession No: M33666.1, Version 1, incorporated herein by reference):

   1 gggcgggcct aggctcatct ccacagggga gaacacacag acagcagaga ccatgggacc   61 cctctcagcc cctccctgca ctcagcacat cacctggaag gggctcctgc tcacagcatc  121 acttttaaac ttctggaacc tgcccaccac tgcccaagta ataattgaag ccaagccacc  181 caaagtttcc gaggggaagg atgttcttct acttgtccac aatttgcccc agaatcttac  241 tggctacatc tggtacaaag ggcaaatgac ggacctctac cattacatta catcatatgt  301 agtacacggt caaattatat atgggcctgc ctacagtgga cgagaaacag tatattccaa  361 tgcatccctg ctgatccaga atgtcacaca ggaggatgca ggatcctaca ccttacacat  421 cataaagcga ggcgatggga ctggaggagt aactggatat ttcactgtca ccttatactc  481 ggagactccc aagccctcca tctccagcag caacttaaac cccagggagg tcatggaggc  541 tgtgcgctta atctgtgatc ctgagactcc ggatgcaagc tacctgtggt tgctgaatgg  601 tcagaacctc cctatgactc acaggttgca gctgtccaaa accaacagga ccctctatct  661 atttggtgtc acaaagtata ttgcaggacc ctatgaatgt gaaatacgga acccagtgag  721 tgccagccgc agtgacccag tcaccctgaa tctcctcccg aagctgccca tgccttacat  781 caccatcaac aacttaaacc ccagggagaa gaaggatgtg ttagccttca cctgtgaacc  841 taagagtcgg aactacacct acatttggtg gctaaatggt cagagcctcc cggtcagtcc  901 gagggtaaag cgacccattg aaaacaggat actcattcta cccagtgtca cgagaaatga  961 aacaggaccc tatcaatgtg aaatacggga ccgatatggt ggcatccgca gtaacccagt 1021 caccctgaat gtcctctatg gtccagacct ccccagaatt tacccttcat tcacctatta 1081 ccgttcagga gaaaacctcg acttgtcctg ctttgcggac tctaacccac cggcagagta 1141 ttcttggaca attaatggga agtttcagct atcaggacaa aagctcttta tcccccaaat 1201 tactacaaat catagcgggc tctatgcttg ctctgttcgt aactcagcca ctggcaagga 1261 aatctccaaa tccatgatag tcaaagtctc tgagacagca tctccccagg ttacctatgc 1321 tggtccaaac acctggtttc aagaaatcct tctgctgtga cctcccaaag tgctaggatt 1381 aaaacatgac ccaccatgaa acccgccca

An exemplary human GABRA3 amino acid sequence is set forth below (SEQ ID NO: 25; GenBank Accession No: AAG12455.1, Version 1, incorporated herein by reference):

  1 miitqtshcy mtslgilfli nilpgttgqg esrrqepgdf vkqdigglsp khapdipdds  61 tdnitiftri ldrlldgydn rlrpglgdav tevktdiyvt sfgpvsdtdm eytidvffrq 121 twhderlkfd gpmkilplnn llaskiwtpd tffhngkksv ahnmttpnkl lrlvdngtll 181 ytmrltihae cpmhledfpm dvhacplkfg syayttaevv yswtlgknks vevaqdgsrl 241 nqydllghvv gteiirsstg eyvvmtthfh lkrkigyfvi qtylpcimtv ilsqvsfwln 301 resvpartvf gvttvltmtt lsisarnslp kvayatamdw fiavcyafvf saliefatvn 361 yftkrswawe gkkvpealem kkktpaapak ktsttfnivg ttypinlakd tefstiskga 421 apsasstpti iaspkatyvq dsptetktyn syskvdkisr iifpvlfaif nlvywatyvn 481 resaikgmir kg

An exemplary human GABRA3 nucleic acid sequence is set forth below (SEQ ID NO: 26; GenBank Accession No: NM_000808.3, Version 3, incorporated herein by reference):

   1 gagagagaga gagagagaga gagagagaga gagcgagaga gcgtgagcgc gcgcaagcta   61 gcgagcaaac cagagagaca gaccgagaga gggaccagga gagagaccca gagagagaag  121 aagaagccag aagccgagct ctgtcagggc tcaacctcca acttgtttca gttcattcat  181 ccttctctcc tttccgctca gactgtagag ctcggtctct ccaagtttgt gcctaagaag  241 atgataatca cacaaacaag tcactgttac atgaccagcc ttgggattct tttcctgatt  301 aatattctcc ctggaaccac tggtcaaggg gaatcaagac gacaagaacc cggggacttt  361 gtgaagcagg acattggcgg gctgtctcct aagcatgccc cagatattcc tgatgacagc  421 actgacaaca tcactatctt caccagaatc ttggatcgtc ttctggacgg ctatgacaac  481 cggctgcgac ctgggcttgg agatgcagtg actgaagtga agactgacat ctacgtgacc  541 agttttggcc ctgtgtcaga cactgacatg gagtacacta ttgatgtatt ttttcggcag  601 acatggcatg atgaaagact gaaatttgat ggccccatga agatccttcc actgaacaat  661 ctcctggcta gtaagatctg gacaccggac accttcttcc acaatggcaa gaaatcagtg  721 gctcataaca tgaccacgcc caacaagctg ctcagattgg tggacaacgg aaccctcctc  781 tatacaatga ggttaacaat tcatgctgag tgtcccatgc atttggaaga ttttcccatg  841 gatgtgcatg cctgcccact gaagtttgga agctatgcct atacaacagc tgaagtggtt  901 tattcttgga ctctcggaaa gaacaaatcc gtggaagtgg cacaggatgg ttctcgcttg  961 aaccagtatg accttttggg ccatgttgtt gggacagaga taatccggtc tagtacagga 1021 gaatatgtcg tcatgacaac ccacttccat ctcaagcgaa aaattggcta ctttgtgatc 1081 cagacctact tgccatgtat catgactgtc attctgtcac aagtgtcgtt ctggctcaac 1141 agagagtctg ttcctgcccg tacagtcttt ggtgtcacca ctgtgcttac catgaccacc 1201 ttgagtatca gtgccagaaa ttccttacct aaagtggcat atgcgacggc catggactgg 1261 ttcatagccg tctgttatgc ctttgtattt tctgcactga ttgaatttgc cactgtcaac 1321 tatttcacca agcggagttg ggcttgggaa ggcaagaagg tgccagaggc cctggagatg 1381 aagaagaaaa caccagcagc cccagcaaag aaaaccagca ctaccttcaa catcgtgggg 1441 accacctatc ccatcaacct ggccaaggac actgaatttt ccaccatctc caagggcgct 1501 gctcccagtg cctcctcaac cccaacaatc attgcttcac ccaaggccac ctacgtgcag 1561 gacagcccga ctgagaccaa gacctacaac agtgtcagca aggttgacaa aatttcccgc 1621 atcatctttc ctgtgctctt tgccatattc aatctggtct attgggccac atatgtcaac 1681 cgggagtcag ctatcaaggg catgatccgc aaacagtaga tagtggtggc agtgcagcaa 1741 ccagagcact gtataccccg tgaagcatcc aggcacccaa accccggggc tccccttcgc 1801 gtatttcagg attctccttt ttacccctct accaagctgt gaccctcaat tcatatttat 1861 gaatctctac gcaaaaaata actacagaaa aattacttgt ccctccaata ttgcccagta 1921 taaccccatc aaagccaaac actgccattt gtccagttgc tcatcttagt ctgccaatct 1981 cccctagctg agggcactgc atgtatttta ttgcactctg cccgctgcaa aaagaacaag 2041 agattctact ctccatagtg gaagccttgg ctgtttgaga ggcccagaac aaggagaatt 2101 gttgactccc atctagatca gatgactcta acttactagg cagccaggtt aggctaggcc 2161 atgtgatcct gcgtgccacc tcccctgcct tcagcaaggc ctactaggca taagtactga 2221 tagcaaaggt gggagccagt tctacacccc caacccattt attggtttgg aaattagtgg 2281 ggacaattgg tactaaccac cgtctaccat gtatggccaa aataaataga actagctctg 2341 ccagcctggc accaagatgg ctggtgccct gccatgtcca gcccctcggg aaaatagtcc 2401 cctccttggt acatctctcc tccagaaaat cttcttcccc cactgccttt ggcacccttg 2461 tagccaactg agcactactt aatttggact cattaccacc tgtaaacttt tcaggaaaaa 2521 atgatcaagc attttttatt tatatcgaaa agttgcaaat agaaacaaag tgatctagat 2581 ttaaaaaaaa cattttttta aaatatggga gagatacaaa agtcacctcc ctgccaaggc 2641 aactagccta tactggattg ggtaagaggt ttggagtgga tggtagttga ggattgaagt 2701 ctggctcaaa agagaaggct actggcagat gaaagtcaaa ttcttccttc catacactcc 2761 acattccaca ccctggccca ggcac

An exemplary human GABRB1 amino acid sequence is set forth below (SEQ ID NO: 27; GenBank Accession No: AAH22449.1, Version 1, incorporated herein by reference):

  1 mwtvqnresl gllsfpvmit mvccahstne psnmsyvket vdrllkgydi rlrpdfggpp  61 vdvgmridva sidmvsevnm dytltmyfqq swkdkrlsys giplnltldn rvadqlcvpd 121 tyflndkksf vhgvtvknrm irlhpdgtvl yglritttaa cmmdlrrypl deqnctleie 181 sygyttddie fywnggegav tgvnkielpq fsivdykmvs kkvefttgay prlslsfrlk 241 rnigyfilqt ympstlitil swvsfwinyd asaarvalgi ttvltmttis thlretlpki 301 pyvkaidiyl mgcfvfvfla lleyafvnyi ffgkgpqkkg askqdqsane knklemnkvq 361 vdahgnills tleirnetsg sevltsysdp katmysydsa siqyrkplss reaygraldr 421 hgvpskgrnr rrasqlkvki pdltdvnsid kwsrmffpit fslfnvvywl yyvh

An exemplary human GABRB1 nucleic acid sequence is set forth below (SEQ ID NO: 28; GenBank Accession No: NM_000812.3, Version 3, incorporated herein by reference):

   1 agccttagcc agatcactga gcgcccagta aaaaaaacaa aatcaggttg agggcagaaa   61 tgaaatcaac atagcaacct ccaatgcatg aaggaaactc cgtttacaca tgctcgtagg  121 atcccctgcg tggaaacagc agcttgtctc tgactacccg gaggacatgg agcaccccaa  181 ataggaactt tagagggatt gaaatctgtt gcctgttcca ctaggaatat tgtttgcaag  241 gcacaaggtg tcttttggta gtgagcgcgc tctgcgcatg cgcaggtcca ttcgggaatt  301 actgcccagc agccgactaa gttgcattcc ttgaatcttc gcagaaaaga caattctttt  361 aatcagagtt agtaatgtgg acagtacaaa atcgagagag tctggggctt ctctctttcc  421 ctgtgatgat taccatggtc tgttgtgcac acagcaccaa tgaacccagc aacatgtcat  481 acgtgaaaga gacagtggac agattgctca aaggatatga cattcgcttg cggccggact  541 tcggagggcc ccccgtcgac gttgggatgc ggatcgatgt cgccagcata gacatggtct  601 ccgaagtgaa tatggattat acactcacca tgtatttcca gcagtcttgg aaagacaaaa  661 ggctttctta ttctggaatc ccactgaacc tcaccctaga caatagggta gctgaccaac  721 tctgggtacc agacacctac tttctgaatg acaagaaatc atttgtgcat ggggtcacag  781 tgaaaaatcg aatgattcga ctgcatcctg atggaacagt tctctatgga ctccgaatca  841 caaccacagc tgcatgtatg atggatcttc gaagatatcc actggatgag cagaactgca  901 ccctggagat cgaaagttat ggctatacca ctgatgacat tgaattttac tggaatggag  961 gagaaggggc agtcactggt gttaataaaa tcgaacttcc tcaattttca attgttgact 1021 acaagatggt gtctaagaag gtggagttca caacaggagc gtatccacga ctgtcactaa 1081 gttttcgtct aaagagaaac attggttact tcattttgca aacctacatg ccttctacac 1141 tgattacaat tctgtcctgg gtgtcttttt ggatcaacta tgatgcatct gcagccagag 1201 tcgcactagg aatcacgaca gtgcttacaa tgacaaccat cagcacccac ctcagggaga 1261 ccctgccaaa gatcccttat gtcaaagcga ttgatattta tctgatgggt tgctttgtgt 1321 ttgtgttcct ggctctgctg gagtatgcct ttgtaaatta catcttcttt gggaaaggcc 1381 ctcagaaaaa gggagctagc aaacaagacc agagtgccaa tgagaagaat aaactggaga 1441 tgaataaagt ccaggtcgac gcccacggta acattctcct cagcaccctg gaaatccgga 1501 atgagacgag tggctcggaa gtgctcacga gcgtgagcga ccccaaggcc accatgtact 1561 cctatgacag cgccagcatc cagtaccgca agcccctgag cagccgcgag gcctacgggc 1621 gcgccctgga ccggcacggg gtacccagca aggggcgcat ccgcaggcgt gcctcccagc 1681 tcaaagtcaa gatccccgac ttgactgatg tgaattccat agacaagtgg tcccgaatgt 1741 ttttccccat caccttttct ctttttaatg tcgtctattg gctttactat gtacactgag 1801 gtctgttcta atggttccat ttagactact ttcctcttct attgtttttt aaccttacag 1861 gtccccaaca gcgatactgc tgtttctcga ggtaagagat tcagccatcc aattggtttt 1921 aggtcttgca tatcagtttt attactgcac catgtttact tcaaaaagac aaaacaaaaa 1981 aaaaattatt tttccagtct accgtggtcc aggttatcag ctctttaaga gctctattaa 2041 ttgccatgtt tacaaacaaa cacaaagaga gaagttagac aggtagatct ttagcagtct 2101 tttctagttt ccctggattt cactgattta ttttttaggg aaaatgaaaa gaggaccttg 2161 ctgtccgcct gcactgcttc ctggtaaact ataacaaact tatgctgcca aaaaaaaaaa 2221 aaaaaa

An exemplary human GABRB2 amino acid sequence is set forth below (SEQ ID NO: 29; GenBank Accession No: AAI05640.1, Version 1, incorporated herein by reference):

  1 mwrvrkrgyf giwsfpliia avcaqsvndp snmslvketv drllkgydir lrpdfggppv  61 avgmnidias idmvsevnmd ytltmyfqqa wrdkrlsynv iplnltldnr vadqlwvpdt 121 yflndkksfv hgvtvknrmi rlhpdgtvly glritttaac mmdlrrypld eqnctleies 181 ygyttddief ywrgddnavt gvtkielpqf sivdyklitk kvvfstgsyp rlslsfklkr 241 nigyfilqty mpsilitils wvsfwinyda saarvalgit tvltmttint hlretlpkip 301 yvkaidmylm gcfvfvfmal leyalvnyif fgrgpqrqkk aaekaasann ekmrldvnkm 361 dphenillst leiknemats eavmglgdpr stmlaydass iqyrkaglpr hsfgrnaler 421 hvaqkksrlr rrasqlkiti pdltdvnaid rwsriffpvv fsffnivywl yyvn

An exemplary human GABRB2 nucleic acid sequence is set forth below (SEQ ID NO: 30; GenBank Accession No: NM_021911.2, Version 2, incorporated herein by reference):

   1 gcgcggggaa gggaagaaga ggacgaggtg gcgcggagac cgcgggagaa cacagtgcct   61 ccggaggaaa tctgctcggt ccccggcagc cgccgcttcc cctttgatgt tttggtacgc  121 cgtgcgcatg cgcctcacat tagaattact gcactgggca gactaagttg gatctcctct  181 cttcagtgaa accctcaatt ccatcaaaaa ctaaagggat gtggagagtg cggaaaaggg  241 gctactttgg gatttggtcc ttccccttaa taatcgccgc tgtctgtgcg cagagtgtca  301 atgaccctag taatatgtcg ctggttaaag agacggtgga tagactcctg aaaggctatg  361 acattcgtct gagaccagat tttggaggtc cccccgtggc tgtggggatg aacattgaca  421 ttgccagcat cgatatggtt tctgaagtca atatggatta taccttgaca atgtactttc  481 aacaagcctg gagagataag aggctgtcct ataatgtaat acctttaaac ttgactctgg  541 acaacagagt ggcagaccag ctctgggtgc ctgataccta tttcctgaac gataagaagt  601 catttgtgca cggagtgact gttaagaacc gcatgattcg cctgcatcct gatggcaccg  661 tcctttatgg actcagaatc acaaccacag ctgcctgcat gatggaccta aggaggtacc  721 cactggatga acaaaactgc accttggaaa ttgagagcta tggatacaca actgatgaca  781 ttgagtttta ctggcgtggc gatgataatg cagtaacagg agtaacgaaa attgaacttc  841 cacagttctc tattgtagat tacaaactta tcaccaagaa ggttgttttt tccacaggtt  901 cctatcccag gttatccctc agctttaagc ttaagagaaa cattggctac tttatcctgc  961 aaacatacat gccttccatc ctgattacca tcctctcctg ggtctccttc tggattaatt 1021 acgatgcttc agctgcaagg gtggcattag gaatcacaac tgtcctcaca atgaccacaa 1081 tcaacaccca cctccgggaa actctcccta aaatccccta tgtgaaggcc attgacatgt 1141 acctgatggg gtgctttgtc ttcgttttca tggcccttct ggaatatgcc ctagtcaact 1201 acatcttctt tgggaggggg ccccaacgcc aaaagaaagc agctgagaag gctgccagtg 1261 ccaacaatga gaagatgcgc ctggatgtca acaagatttt ttataaagat attaaacaaa 1321 atgggaccca atatcgatcc ttgtgggacc ctactggaaa cctctcccca actagacgga 1381 ctaccaatta cgatttctct ctgtatacga tggaccccca tgagaacatc ttactgagca 1441 ctctcgagat aaaaaatgaa atggccacat ctgaggctgt gatgggactt ggagacccca 1501 gaagcacaat gctagcctat gatgcctcca gcatccagta tcggaaagct gggttgccca 1561 ggcatagttt tggccgaaat gctctggaac gacatgtggc gcaaaagaaa agtcgcctga 1621 ggagacgcgc ctcccaactg aaaatcacca tccctgactt gactgatgtg aatgccatag 1681 atcggtggtc ccgcatattc ttcccagtgg ttttttcctt cttcaacatc gtctattggc 1741 tttattatgt gaactaaaac atggcctccc actggaagca aggactagat tcctcctcaa 1801 accagttgta cagcctgatg taggacttgg aaaacacatc aatccaggac aaaagtgacg 1861 ctaaaatacc ttagttgctg gcctatcctg tggtccattt cataccattt gggttgcttc 1921 tgctaagtaa tgaatacact aaggtccttg tggttttcca gttaaaacgc aagtgatttt 1981 tacacatggt ggctagacag cctgagtgct ccatgttgtc tgtttagtat gcagcctact 2041 cagaggggaa taatttggaa gatattctta gaaggctcaa cagcattgtc agtcatttgg 2101 tcataaccag atactcctca tcttcctttt taaggtcggc atgctgttga gatggcattg 2161 tccttatgaa acattatctg taatgccatg caaacacatt acttgaagat gatctatgat 2221 tttcttactg agatgataat ggtgtcatgg gaagattatt cccactggtt tctaaaagat 2281 tctcttgtga tttgagcagg ctaggggaat caagacagag actcaggaaa ccgatttggc 2341 cagtcccttt gcttgagcac ggagaatcaa ctatgatgtc tttcattttg gcatttagag 2401 atgaggagac ttctggacaa tatcatgcat ggtggccaag aaaatttttg ctaaacggct 2461 atttcctagg tggttaaagt aagagttaac aacacagagc agagtagaaa atcagaaacg 2521 acggttgtaa caaaaagcaa gcaagcaaga aagcatgacc cttatcagct ccacacagca 2581 tctggtctat acatactgtg tctagtggca gagggtgagt aagagagatt gtttttccaa 2641 catcactagc ttttgacagc atacctaaag aggtttttat agtttaatcg aagataacca 2701 tgaaatacaa aaattagaga aatgagaatt gtcttagata ttcaggttag attcagagtc 2761 attcaaatat acaaatacag agcacaaact agcaaacaga ttgtttttct cagacgaagt 2821 cagctgtccc tgcaattttt gtccctataa ttttatttct taatttaata gagtatttca 2881 agagaaggat ttgttcatca ctttaaagga ttcatggtcc tctccagctt tttttttgct 2941 tccaaaattc tgattatatt cttaggagac tggcaaagta aggctttgga gagattgagt 3001 gaactatatt ttcttatatg caatgaaatt caccattgta tttttcaaag caaataatac 3061 ttcaaggagt atgaacacac agagagttaa tttgtgcatt cattggtttg gggcttgatt 3121 ttcttaagag tgctttcatt gtatatgttg caatctgcct aatcaaggaa aatatgaaaa 3181 ctagtggaaa ataataacaa agccacatta acatgataaa tgttatgagc ctcagttgat 3241 attgcagaaa aatatataac tgttaatcag gcaggcatga tgtatttttt ttctattttt 3301 aagttatgcc attgtgcttc tttctacact aattggacat aagcattcat atgttggaca 3361 agaggagaat aagctaatat gtcttccttc tatcaatata aggctcatat tttgcttttc 3421 ttatagaaaa tagtgaattg ctaaattttc cttaaagttg aatttgattg aactttttct 3481 tggaggatga ctttgctatt tctattttga aaacaaagaa agctcttctt tttagagtaa 3541 tatccctaat tgtgcatagc agccagtatc cacctgtgaa taatgtatgt tttcttgatt 3601 ccttgtttcc ttcatgattt agcagcttgg aatatgatgg agtactattg cccttgcatt 3661 ccagctgtcc aagaacaaca acaaaccttt atccttcagc tttctgaatt tgccccaaaa 3721 tggaatggta ttttgttttt caccagtgta ggaaaccttg gccattatat tttgattaca 3781 taatcttgag cacctctgag tatcatcttt gggcagaatc tgaccaagat tcttctcaca 3841 ggctcagagt agagattcct catgtttctc caggacacac tttctcctag gcaatcattt 3901 tggggcatca cactaagtaa agtgcctgcc ccttgtcaac agggggtaaa gtttgactaa 3961 aaaacatcag gaaggaacat attgataact caggggcaca actccaaaat gccattctga 4021 aaaggctctt ctagagtcaa ctcagagccc aagtgtagaa gtgggctctt atgtgcaatc 4081 actgtacaag ccataaaaat ctttgatatt gccatttatg attacaacaa aattttagat 4141 gtccaagaaa gtcaacagaa caatccagat caaagtgtag agaagcatct ttgcagcttg 4201 agcctcaaaa gcataaaacc aggaattcat ttctgctctc agtgatacaa gaaacaaggc 4261 aaaggaaaaa agatgggacc ttagaagcaa tgccctagag taaaaagcat acattggcac 4321 tcagtaacca cagagataga aacaactgac tcagcctctc cagaaataac agtagatgta 4381 gaatttgttc ttaaatatat gtttcgttga aatgaaatgc agtcatcaaa tgcgaggagg 4441 ggtgctagac ctgataagtc taggaagacc agtcagcttg atagccagtt gttaaactaa 4501 aggaccacaa aggtgtgttt agtagttctg atatgggatt actatcagtt tatacatatg 4561 tatagatttt cttttaatta taaacagcca gatagccagc aattaaggtg ttttttcatc 4621 tttgtgaaat tcatggacaa attctgactc taaaatgcac agtctacatg aaatctttga 4681 tctcaatctg tatatatata tattgtacat gaccgctagt aggtatgaaa tgcatttcag 4741 agttgaaaac tcatgcaaca taatcatgtg tttgcataag gaatgttaaa attctttcta 4801 ctacaattta ttaacagggg aaaagattca agcagtgcca tctagacctt ttctcttctc 4861 atttcttcaa aagcagtgct aagtaaaata ataataataa aaatggttta tgaaccaaaa 4921 gactttacat tctagcatta ggaacacaca caaaaaaatc tgtcagctta caaaagcaca 4981 acacataaag aaagagcagt ggaatgcgta atggggaaat gaatcatgtt taaagcaaga 5041 cttgcattaa attggcaact aagataattt ccattttcta taggtaaccg tgttccagtt 5101 taatgattac cttcatactc aacaagaaaa atggcaaagc aacatcatca aaataggtct 5161 tacaacatat ctacatgtat atatgtgtat atatagattc atataaacat acatacatat 5221 atatgcattc atatgttgga aaacaaaagg aataagctaa tatgttttat ttccttcatt 5281 aaaccagtat atgagtattt ttaatttggc aaacaaaaat caacatactg aaataagtaa 5341 tacagggtac tgagcatttc tctatcagca aatcaatgcc tacagttttt atgaaccatt 5401 gcacagttca actcgacaat agtactgtac cccagaacat cagaagttaa gtagttgtca 5461 cattgcttgt ctaattgctc tctttttcaa ggaaacaaat aacattgtcc attggtgagt 5521 caaaaacaaa catgtcttaa gaaaatgaaa aatgataaaa attcctccaa agaggaagaa 5581 aaaaaaaaaa ctaaacccca ccatgttggt tagggcaaaa tactaagtat tcacaactgt 5641 agcaatcatg ccatttggct aaatgtacag agtacatgta atgtgagcaa ccataacttt 5701 cactgaacgt gtgtaaatat taaaacagat ttcttaaata tttttaactt ctaatttgta 5761 ttttatggta aggcaatgtg ctaattccgt ttatggctta agttgatgtg ttataatatg 5821 taaataatta aacatgctgt aaatgaatag tcaatagata caaataattg tttagttttt 5881 ttcttaattt ttatttattt tttactaagt actattactg cagtgccccc agcagagtaa 5941 tttaaacacc cttttgcata aatggtttgg gaatcccaga cagaagggtt tcaatttgct 6001 atcacacaca cagtcacaca cagtcacaca cacacacaca cacacactca aacacacata 6061 atcttttgct cacccactct gtctctctgc ccgtctatgg gaaacactct actatttatg 6121 tagtcaatat aacaaacaag agatagcctt tgaaatggca attgggaaaa gcaaaaatga 6181 tcattgataa cttaatagac ttttttatat gtcagagttc aagaaaccaa agtttgcaac 6241 ttaaatctca gttttcaaac agtaaaagtt tgtatagatg gcactacaga aaaataaaaa 6301 tggttattcc taccagctcc agaaatgtgt tacacaatat acactagaag actttttttt 6361 taataatagt attttgtcct taggtagtat tgttcctttc aaccaaagac tccagaatta 6421 ttgaaaaaca aaaaaggaaa aaaaaaatga gataatgggg gaaaaaaagg acgctgcttc 6481 acaccaaagg tttaaaaaaa tattttccaa atgcactagg aacattgtaa aaaccagaaa 6541 ggagtgaaca gaatgctaat gaagatactg ccctaaagaa atctgtacaa aaaaaaaaaa 6601 aaaaagcagc actcttaaaa agctactagg tttttggaaa ttgaagtaaa atatttctgt 6661 agatatattc aaaattctga catcaaattt taatttgctt aaagaagttt tatttgtgat 6721 gaagatcaat atgattcaaa tgatgaaaaa caaaactgta tgtcctttga gttcccaaac 6781 caaatgtcac tgccgtgtca catcctctaa tctgatgccc atgtgtgtgt ccttgcgcca 6841 tttgaagcaa gttgacagtt ccatcagttt gtttttgttt ttgtttttgg ttcaataatt 6901 tgagttcaac catcgtcatt ttaaacataa ttaatcccaa caaagttgcc tatagtttaa 6961 tttaaacctc acagcatttt taatttattt tgcatgggtg tttaaatagt tctgttacga 7021 atattgtccc tgcacagttc taaattgtcc ttttataaaa aaaaaaagtg atattctagt 7081 ttcttcacaa tgtagtgatt atcagcctta ctaattacct tgtagccttt cttaatatgc 7141 acataatgca cattttccga tggctagaaa aatgcaaaac acagtggata tcattgcatc 7201 tattttcatg tctttctaaa aacaggacta ttaaaatctc tgggatacat gagatagtaa 7261 aaaatgagga ttataaatga atagcacata agaattattt tcttgaattt aaacttattg 7321 cagccagttt cagcatgtaa atatataata atgttggcta gtgtgtaatt cttgaactaa 7381 gaaatataaa taaaaataaa aagattgtg

An exemplary human GABRG2 amino acid sequence is set forth below (SEQ ID NO: 31; GenBank Accession No: AAD50273.1, Version 1, incorporated herein by reference):

  1 msspniwstg ssvystpvfs qkmtvwilll lslypgftsq ksdddyedya snktwvltpk  61 vpegdvtvil nnllegydnk lrpdigvkpt lihtdmyvns igpvnainme ytidiffaqt 121 wydrrlkfns tikvlrinsn mvgkiwipdt ffrnskkada hwittpnrml riwndgrvly 181 tlrltidaec qlqlhnfpmd ehscplefss ygypreeivy qwkrssvevg dtrswrlyqf 241 sfvglrntte vvkttsgdyv vmsvyfdlsr rmgyftiqty ipctlivvls wvsfwinkda 301 vpartslgit tvltmttlst iarkslpkvs yvtamdlfvs vcfifvfsal veygtlhyfv 361 snrkpskdkd kkkknpapti dirprsatiq mnnathlqer deeygyecld gkdcasffcc 421 fedcrtgawr hgrihiriak mdsyariffp tafclfnlvy wvsylyl

An exemplary human GABRG2 nucleic acid sequence is set forth below (SEQ ID NO: 32; GenBank Accession No: NM_198904.2, Version 2, incorporated herein by reference):

   1 gtaagtgtga ggggcatgag tatacacgag tgtgcgtgtc tttccctctc ccttatttgt   61 ctccgtatga gtctctcctt gtaccctccc cctgcctcga tgatattact cccccagact  121 tggaagccgc tgccagagtg acgctttgat ggtatctgca agcgtttttg ctgatcttat  181 ctctgccccc tgaatattaa ttccctaatc tggtagcaat ccatctcccc agtgaaggac  241 ctactagagg caggtggggg gagccaccat cagatcataa gcataagaat aatacaaagg  301 ggagggattc ttctgcaacc aagaggcaag aggcgagaga aggaaaaaaa aaaaagcgat  361 gagttcgcca aatatatgga gcacaggaag ctcagtctac tcgactcctg tattttcaca  421 gaaaatgacg gtgtggattc tgctcctgct gtcgctctac cctggcttca ctagccagaa  481 atctgatgat gactatgaag attatgcttc taacaaaaca tgggtcttga ctccaaaagt  541 tcctgagggt gatgtcactg tcatcttaaa caacctgctg gaaggatatg acaataaact  601 tcggcctgat ataggagtga agccaacgtt aattcacaca gacatgtatg tgaatagcat  661 tggtccagtg aacgctatca atatggaata cactattgat atattttttg cgcaaacgtg  721 gtatgacaga cgtttgaaat ttaacagcac cattaaagtc ctccgattga acagcaacat  781 ggtggggaaa atctggattc cagacacttt cttcagaaat tccaaaaaag ctgatgcaca  841 ctggatcacc acccccaaca ggatgctgag aatttggaat gatggtcgag tgctctacac  901 cctaaggttg acaattgatg ctgagtgcca attacaattg cacaactttc caatggatga  961 acactcctgc cccttggagt tctccagtta tggctatcca cgtgaagaaa ttgtttatca 1021 atggaagcga agttctgttg aagtgggcga cacaagatcc tggaggcttt atcaattctc 1081 atttgttggt ctaagaaata ccaccgaagt agtgaagaca acttccggag attatgtggt 1141 catgtctgtc tactttgatc tgagcagaag aatgggatac tttaccatcc agacctatat 1201 cccctgcaca ctcattgtcg tcctatcctg ggtgtctttc tggatcaata aggatgctgt 1261 tccagccaga acatctttag gtatcaccac tgtcctgaca atgaccaccc tcagcaccat 1321 tgcccggaaa tcgctcccca aggtctccta tgtcacagcg atggatctct ttgtatctgt 1381 ttgtttcatc tttgtcttct ctgctctggt ggagtatggc accttgcatt attttgtcag 1441 caaccggaaa ccaagcaagg acaaagataa aaagaagaaa aaccctcttc ttcggatgtt 1501 ttccttcaag gcccctacca ttgatatccg cccaagatca gcaaccattc aaatgaataa 1561 tgctacacac cttcaagaga gagatgaaga gtacggctat gagtgtctgg acggcaagga 1621 ctgtgccagt tttttctgct gttttgaaga ttgtcgaaca ggagcttgga gacatgggag 1681 gatacatatc cgcattgcca aaatggactc ctatgctcgg atcttcttcc ccactgcctt 1741 ctgcctgttt aatctggtct attgggtctc ctacctctac ctgtgaggag gtatgggttt 1801 tactgatatg gttcttattc actgagtctc atggagagat gtctgttcta agtccactta 1861 aataatcctc tatgtggttg ataatgatct gaatctgttt ctatgtccaa acctggtaaa 1921 ttttataatg tcatattgtt tgtgcccagc cctcctttgg ttagtgtact ttgaacttcg 1981 atgtttgctg tgtttcaaac ctgcaaggca aagtaaaatt agagcaagaa cattcaaacc 2041 aaataagata tttttcagct acagcaaata aaacagtgaa agccctgact atttacagta 2101 gtggtatcct tactagattc ataatgcaat tagatagaaa aggtccaaaa ctgtacccta 2161 tgttcactcc gggtcaagtt gtgataaatt tgatcccaat agaatacctc cctcatttaa 2221 gaaaaatcat aactcacttt aaatatgaaa gcctagtcca gaaatctatt acacctttat 2281 ctcaagatag gaagaaaatt tcctccacat tcatgtacaa tgatgtaaat atttcaataa 2341 cttagaatgc ttcaagttta gtgcatgcat ctctttagat ccaaaataaa tggactgaag 2401 ttatcatcct attgtctttt attttgtgtc cttgggctat aaaagattcc tgaatgtaat 2461 tataaggatt tgggtttgga aatggaggga ggaattttca ttgccttctc cctcatgcat 2521 gaagattcga acagcttatt ttttccttgt atgacatatt acaacacttt aagtaaaata 2581 tagactggat aatcaacatt tgccacctct aaatatgccc aatttcataa ctagagtata 2641 aagtaattgt atgtgcttgc cgctattttt ttcttccttt taggatgata gatcataaca 2701 gaacttattc tccatctcaa gatctgcttc tagtgattgt gagtgccttg tgggcagaat 2761 ccttgtcatt tcctctttgg gtctgtagca ccttgcatag tgcctggcat atagttggtg 2821 ctcaataaat atggtttgaa gtgaattgcc ctcacatgct tctggcaaat ctctgtgctg 2881 gcctgaaacc agtgactcat cttctcacat aggtgttgtc aagtgatatt tgattttgta 2941 aaaataacca gtaggatcca aagaacttta gctatttatg ttcatcttca aaaaattatt 3001 ttaggcaaag tccatactcc ttttaaaaca atatttatgt cctatgtttg tgtatagaca 3061 tgactctact agggcataat tagagtttgt gtattatttt tccaggtttg gggatgagtc 3121 agtccttgcc catccacaat tttgtttgtg aacttataac aggaataagc aaaattcata 3181 cctgactagt gttcagaatg tagcattctg tgcgaaaaag tattgaagat tagcttttaa 3241 aaactgaaaa aaaaaaatga atgactcaca tagaggttga gccaatgact gtggcctcat 3301 tagattacat tgtagttaaa caaagcaatt tctccagact taaaacatga tgagttgagc 3361 tctatcttca tgtactcatc ctgaatcctt atttttctaa aatagcaccc tttgttaatt 3421 atttttatgg aaattattac tctgtcataa ttaaatcata gctagtataa ctttacagat 3481 aacctaaaaa gaatagaaaa gaagagagag tggctttgtc agtataaaac catgtaaagt 3541 catcatcaag tcatctggat gaatcttgaa acacatttag ctgccagttt tacaaacctt 3601 taatatatca gtgctccagt atataacctc aaacaaatgt aaatagaacg aattattttc 3661 ttgttttgaa ttgtcaatat attaaatgtt gactctttgg gagagttgtt ggcaagtttc 3721 aatggtgaga aacattattg tcaacttgaa atgtgttctg taatggggac actacaaaaa 3781 gctagctttc caatgtgtgc atagtattgg caatatgaat atatattata tataatctaa 3841 tacttattat aagctgctcc ctgtctatgt atttggaaac cttttcacaa agggaattgc 3901 ctaacatgtg gacttttaca ataaaaatgc tgcattctaa tccatggtgg catctca

An exemplary human GABRQ amino acid sequence is set forth below (SEQ ID NO: 33; GenBank Accession No: EAW99424.1, Version 1, incorporated herein by reference):

  1 mgirgmlraa villlirtwl aegnypspip kfhfefssav pevvlnlfnc kncaneavvq  61 kildrvlsry dvrlrpnfgg apvpvrisiy vtsieqisem nmdytitmff hqtwkdsrla 121 yyettlnltl dyrmheklwv pdcyflnskd afvhdvtven rvfqlhpdgt vrygirlttt 181 aacsldlhkf pmdkqacnlv vesygytved iilfwddngn aihmteelhi pqftflgrti 241 tskevyfytg syirlilkfq vqrevnsylv qvywptvltt itswisfwmn ydssaarvti 301 gltsmliltt idshlrdklp niscikaidi yilvclffvf lslleyvyin ylfysrgprr 361 qprrhrrprr viaryryqqv vvgnvqdgli nvedgvsslp itpaqaplas peslgsltst 421 seqaqlatse slspltslsg qaplatgesl sdlpstseqa rhsygvrfng fqaddsifpt 481 eirnrveahg hgvthdheds neslssderh ghgpsgkpml hhgekgvqea gwdlddnndk 541 sdclaikeqf kcdtnstwgl nddelmahgq ekdsssesed scppspgcsf tegfsfdlfn 601 pdyvpkvdkw srflfplafg lfnivywvyh my

An exemplary human GABRQ nucleic acid sequence is set forth below (SEQ ID NO: 34; GenBank Accession No: NM_018558.3, Version 3, incorporated herein by reference):

   1 gcgcccagaa cgccccggcc atgggcatcc gaggcatgct gcgagccgca gtgatcctgc   61 tgctcatcag gacctggctc gcggagggca actaccccag tcccatcccg aaattccact  121 tcgagttctc ctctgctgtg cccgaagtcg tcctgaacct cttcaactgc aaaaattgtg  181 caaatgaagc tgtggttcaa aagattttgg acagggtgct gtcaagatac gatgtccgcc  241 tgagaccgaa ttttggaggt gcccctgtgc ctgtgagaat atctatttat gtcacgagca  301 ttgaacagat ctcagaaatg aatatggact acacgatcac gatgtttttt catcagactt  361 ggaaagattc acgcttagca tactatgaga ccaccctgaa cttgaccctg gactatcgga  421 tgcatgagaa gttgtgggtc cctgactgct actttctgaa cagcaaggat gctttcgtgc  481 atgatgtgac tgtggagaat cgcgtgtttc agcttcaccc agatggaacg gtgcggtacg  541 gcatccgact caccactaca gcagcttgtt ccctggatct gcataaattc cctatggaca  601 agcaggcctg caacctggtg gtagagagct atggttacac ggttgaagac atcatattat  661 tctgggatga caatgggaac gccatccaca tgactgagga gctgcatatc cctcagttca  721 ctttcctggg aaggacgatt actagcaagg aggtgtattt ctacacaggt tcctacatac  781 gcctgatact gaagttccag gttcagaggg aagttaacag ctaccttgtg caagtctact  841 ggcctactgt cctcaccact attacctctt ggatatcgtt ttggatgaac tatgattcct  901 ctgcagccag ggtgacaatt ggcttaactt caatgctcat cctgaccacc atcgactcac  961 atctgcggga taagctcccc aacatttcct gtatcaaggc cattgatatc tatatcctcg 1021 tgtgcttgtt ctttgtgttc ctgtccttgc tggagtatgt ctacatcaac tatcttttct 1081 acagtcgagg acctcggcgc cagcctaggc gacacaggag accccgaaga gtcattgccc 1141 gctaccgcta ccagcaagtg gtggtaggaa acgtgcagga tggcctgatt aacgtggaag 1201 acggagtcag ctctctcccc atcaccccag cgcaggcccc cctggcaagc ccggaaagcc 1261 tcggttcttt gacgtccacc tccgagcagg cccagctggc cacctcggaa agcctcagcc 1321 cactcacttc tctctcaggc caggcccccc tggccactgg agaaagcctg agcgatctcc 1381 cctccacctc agagcaggcc cggcacagct atggtgttcg ctttaatggt ttccaggctg 1441 atgacagtat tattcctacc gaaatccgca accgtgtcga agcccatggc catggtgtta 1501 cccatgacca tgaagattcc aatgagagct tgagctcgga tgagcgccat ggccatggcc 1561 ccagtgggaa gcccatgctt caccatggcg agaagggtgt gcaagaagca ggctgggacc 1621 ttgatgacaa caatgacaag agcgactgcc ttgccattaa ggagcaattc aagtgtgata 1681 ctaacagtac ctggggcctt aatgatgatg agctcatggc ccatggccaa gagaaggaca 1741 gtagctcaga gtctgaggat agttgccccc caagccctgg gtgctccttc actgaagggt 1801 tctccttcga tctctttaat cctgactacg tcccaaaggt cgacaagtgg tcccggttcc 1861 tcttccctct ggcctttggg ttgttcaaca ttgtttactg ggtataccat atgtattagt 1921 cccccagtgc tccagaacag cgggagcact gtgctgtgct cctttcagtt tcttttgggt 1981 ttgtttttcc ctctttcctt

An exemplary human GABRR1 amino acid sequence is set forth below (SEQ ID NO: 35; GenBank Accession No: EAW48558.1, Version 1, incorporated herein by reference):

  1 mlavpnmrfg ifllwwgwvl atesrmhwpg revhemskkg rpqrqrrevh edahkqvspi  61 lrrspditks pltkseqllr iddhdfsmrp gfggpaipvg vdvqveslds isevdmdftm 121 tlylrhywkd erlsfpstnn lsmtfdgrlv kkiwvpdmff vhskrsfihd tttdnvmlrv 181 qpdgkvlysl rvtvtamcnm dfsrfpldtq tcsleiesya yteddlmlyw kkgndslktd 241 erislsqfli qefhtttkla fysstgwynr lyinftlrrh ifffllqtyf patlmvmlsw 301 vsfwidrrav parvplgitt vltmstiitg vnasmprvsy ikavdiylwv sfvfvflsvl 361 eyaavnyltt vqerkeqklr eklpctsglp pprtamldgn ysdgevndld nympengekp 421 drmmvqltla sersspqrks qrssyvsmri dthaidkysr iifpaayilf nliywsifs

An exemplary human GABRR1 nucleic acid sequence is set forth below (SEQ ID NO: 36; GenBank Accession No: NM_002042.4, Version 4, incorporated herein by reference):

   1 taataatggc cgtaagctta aaatagatcc agggaggagc tcattaacgt gaacatagaa   61 agcagttccg cacctctggc cttactcctc ttggaaattg ctttggtcca tttttacttc  121 cttttattcg acgcaccaga aaataagact tttaccaaca tttttactgc atttgacgat  181 gaactaattt agaccggcta aaataattgt tccactggga cacaggaatt caacctcagt  241 tcagaaaatc cctgacatct gacgtaggag gatttatagg tttagtggaa attgctttct  301 cctgctctcc agattgcatc ctgtgggttg attttttttt tgcatgagta aacatccttc  361 taataatgaa cagaccaata atgtcttaag agagaaaaag aacaatcttt tcctttttgc  421 tgtttctgga gagagctgtt tgaatttgga aacccatgtt ggctgtccca aatatgagat  481 ttggcatctt tcttttgtgg tggggatggg ttttggccac tgaaagcaga atgcactggc  541 ccggaagaga agtccacgag atgtctaaga aaggcaggcc ccaaagacaa agacgagaag  601 tacatgaaga tgcccacaag caagtcagcc caattctgag acgaagtcct gacatcacca  661 aatcgcctct gacaaagtca gaacagcttc tgaggataga tgaccatgat ttcagcatga  721 ggcctggctt tggaggccct gccattcctg ttggtgtgga tgtgcaggtg gagagtttgg  781 atagcatctc agaggttgac atggacttta cgatgaccct ctacctgagg cactactgga  841 aggacgagag gctgtctttt ccaagcacca acaacctcag catgacgttt gacggccggc  901 tggtcaagaa gatctgggtc cctgacatgt ttttcgtgca ctccaaacgc tccttcatcc  961 acgacaccac cacagacaac gtcatgttgc gggtccagcc tgatgggaaa gtgctctata 1021 gtctcagggt tacagtaact gcaatgtgca acatggactt cagccgattt cccttggaca 1081 cacaaacgtg ctctcttgaa attgaaagct atgcctatac agaagatgac ctcatgctgt 1141 actggaaaaa gggcaatgac tccttaaaga cagatgaacg gatctcactc tcccagttcc 1201 tcattcagga attccacacc accaccaaac tggctttcta cagcagcaca ggctggtaca 1261 accgtctcta cattaatttc acgttgcgtc gccacatctt cttcttcttg ctccaaactt 1321 atttccccgc taccctgatg gtcatgctgt cctgggtgtc cttctggatc gaccgcagag 1381 ccgtgcctgc cagagtcccc ttaggtatca caacggtgct gaccatgtcc accatcatca 1441 cgggcgtgaa tgcctccatg ccgcgcgtct cctacatcaa ggccgtggac atctacctct 1501 gggtcagctt tgtgttcgtg ttcctctcgg tgctggagta tgcggccgtc aactacctga 1561 ccactgtgca ggagaggaag gaacagaagc tgcgggagaa gcttccctgc accagcggat 1621 tacctccgcc ccgcactgcg atgctggacg gcaactacag tgatggggag gtgaatgacc 1681 tggacaacta catgccagag aatggagaga agcccgacag gatgatggtg cagctgaccc 1741 tggcctcaga gaggagctcc ccacagagga aaagtcagag aagcagctat gtgagcatga 1801 gaatcgacac ccacgccatt gataaatact ccaggatcat ctttccagca gcatacattt 1861 tattcaattt aatatactgg tctattttct cctagatgct tgtaattcta caaatttcac 1921 atttccatgg catgcactac agaaataact gtataatgaa aaagtattta aggatatggt 1981 taaaaaaaaa tcccaggacc cacccatgtt ttcactatcc cttctgcagc tttccaaagc 2041 tacattgacg agacacttac tggtttaatt tgcacttatt aaccatctat tgaatacaca 2101 gcattatatt aggtgctgca ggaaatacga cactgtagcg actgatgtta gttgttaccc 2161 agatcccctg gaaaagcaca ctaccagtgt tgtgggcaca tttagttcca cccgttagac 2221 ccttgatgct attcacatga ataatttatt ttcctcaagt gtcattacat tgttcaggct 2281 acgtgaactt ggaagcacct acaggccatt tgcatgaaat tcacatgcac ctaaatcctc 2341 actttgacag aaactcatgc ttcagtttat aacctattac ctattttgta tgcgactcca 2401 cctccgcatg tttattttaa taaaaggcaa tgataacatt cacattattt ttctttatat 2461 gctgtggttc acaggcttta ccccttcaca agaaaagctc tttagattgg cgcaattgct 2521 tctgattttg gtgaaatttt ccctggtagg gaaactttga agataagagt acacacatgc 2581 attttgtctg ttgtgtcata gaggtaacta ggctagaaaa tttgtgttta aatgttccct 2641 attttatata atcaccactt catgtttctt cttcttggag catgtccttg ttcaaagaga 2701 agtgctttct cagtgatgtg atatcttcac tgaggaactt gggtagagaa tgatttcttc 2761 tgcataaaca cttcaaggaa atacataatt tgggactact tgtaactcat tagaatgaga 2821 aatactcaca tggtttctta agagaaaaag aacatcggaa agcaaaataa atgggaagat 2881 atcactggac atctgcattt atactcgaaa taccagcatt ttctatggac cagaaaactg 2941 ccatcaccta gaccacacag cccagatacc aggcagacgg atggcccaat ggcaactgat 3001 gtcagggcat ggggtaaagg agagggttct aatctggtgt atcacttaaa aacagttatt 3061 tatattatat atctgctata tagatcaacc tccaccaaac ttacccaaac agcatttgtt 3121 ttatttgaaa ctcactttaa taaagtgaat tatatacaca aaaaaaaaaa aaaa

An exemplary human CLDN1 amino acid sequence is set forth below (SEQ ID NO: 37; GenBank Accession No: CAG33419.1, Version 1, incorporated herein by reference):

  1 managlqllg filaflgwig aivstalpqw riysyagdni vtaqamyegl wmscvsqstg  61 qiqckvfdsl lnlsstlqat ralmvvgill gviaifvatv gmkcmkcled devqkmrmav 121 iggaifllag lailvatawy gnrivqefyd pmtpvnarye fgqalftgwa aaslcllgga 181 llccscprkt tsyptprpyp kpapssgkdy v

An exemplary human CLDN1 nucleic acid sequence is set forth below (SEQ ID NO: 38; GenBank Accession No: NM_021101.4, Version 4, incorporated herein by reference):

   1 gtctcagttc ccgagcctgg gagcaaccgc agcttctagt atccagactc cagcgccgcc   61 ccgggcgcgg accccaaccc cgacccagag cttctccagc ggcggcgcag cgagcagggc  121 tccccgcctt aacttcctcc gcggggccca gccaccttcg ggagtccggg ttgcccacct  181 gcaaactctc cgccttctgc acctgccacc cctgagccag cgcgggcgcc cgagcgagtc  241 atggccaacg cggggctgca gctgttgggc ttcattctcg ccttcctggg atggatcggc  301 gccatcgtca gcactgccct gccccagtgg aggatttact cctatgccgg cgacaacatc  361 gtgaccgccc aggccatgta cgaggggctg tggatgtcct gcgtgtcgca gagcaccggg  421 cagatccagt gcaaagtctt tgactccttg ctgaatctga gcagcacatt gcaagcaacc  481 cgtgccttga tggtggttgg catcctcctg ggagtgatag caatctttgt ggccaccgtt  541 ggcatgaagt gtatgaagtg cttggaagac gatgaggtgc agaagatgag gatggctgtc  601 attgggggtg cgatatttct tcttgcaggt ctggctattt tagttgccac agcatggtat  661 ggcaatagaa tcgttcaaga attctatgac cctatgaccc cagtcaatgc caggtacgaa  721 tttggtcagg ctctcttcac tggctgggct gctgcttctc tctgccttct gggaggtgcc  781 ctactttgct gttcctgtcc ccgaaaaaca acctcttacc caacaccaag gccctatcca  841 aaacctgcac cttccagcgg gaaagactac gtgtgacaca gaggcaaaag gagaaaatca  901 tgttgaaaca aaccgaaaat ggacattgag atactatcat taacattagg accttagaat  961 tttgggtatt gtaatctgaa gtatggtatt acaaaacaaa caaacaaaca aaaaacccat 1021 gtgttaaaat actcagtgct aaacatggct taatcttatt ttatcttctt tcctcaatat 1081 aggagggaag atttttccat ttgtattact gcttcccatt gagtaatcat actcaactgg 1141 gggaaggggt gctccttaaa tatatataga tatgtatata tacatgtttt tctattaaaa 1201 atagacagta aaatactatt ctcattatgt tgatactagc atacttaaaa tatctctaaa 1261 ataggtaaat gtatttaatt ccatattgat gaagatgttt attggtatat tttctttttc 1321 gtctatatat acatatgtaa cagtcaaata tcatttactc ttcttcatta gctttgggtg 1381 cctttgccac aagacctagc ctaatttacc aaggatgaat tctttcaatt cttcatgcgt 1441 gcccttttca tatacttatt ttatttttta ccataatctt atagcacttg catcgttatt 1501 aagcccttat ttgttttgtg tttcattggt ctctatctcc tgaatctaac acatttcata 1561 gcctacattt tagtttctaa agccaagaag aatttattac aaatcagaac tttggaggca 1621 aatctttctg catgaccaaa gtgataaatt cctgttgacc ttcccacaca atccctgtac 1681 tctgacccat agcactcttg tttgctttga aaatatttgt ccaattgagt agctgcatgc 1741 tgttccccca ggtgttgtaa cacaacttta ttgattgaat ttttaagcta cttattcata 1801 gttttatatc cccctaaact acctttttgt tccccattcc ttaattgtat tgttttccca 1861 agtgtaatta tcatgcgttt tatatcttcc taataaggtg tggtctgttt gtctgaacaa 1921 agtgctagac tttctggagt gataatctgg tgacaaatat tctctctgta gctgtaagca 1981 agtcacttaa tctttctacc tcttttttct atctgccaaa ttgagataat gatacttaac 2041 cagttagaag aggtagtgtg aatattaatt agtttatatt actctcattc tttgaacatg 2101 aactatgcct atgtagtgtc tttatttgct cagctggctg agacactgaa gaagtcactg 2161 aacaaaacct acacacgtac cttcatgtga ttcactgcct tcctctctct accagtctat 2221 ttccactgaa caaaacctac acacatacct tcatgtggtt cagtgccttc ctctctctac 2281 cagtctattt ccactgaaca aaacctacgc acataccttc atgtggctca gtgccttcct 2341 ctctctacca gtctatttcc attctttcag ctgtgtctga catgtttgtg ctctgttcca 2401 ttttaacaac tgctcttact tttccagtct gtacagaatg ctatttcact tgagcaagat 2461 gatgtaatgg aaagggtgtt ggcattggtg tctggagacc tggatttgag tcttggtgct 2521 atcaatcacc gtctgtgttt gagcaaggca tttggctgct gtaagcttat tgcttcatct 2581 gtaagcggtg gtttgtaatt cctgatcttc ccacctcaca gtgatgttgt ggggatccag 2641 tgagatagaa tacatgtaag tgtggttttg taatttaaaa agtgctatac taagggaaag 2701 aattgaggaa ttaactgcat acgttttggt gttgcttttc aaatgtttga aaacaaaaaa 2761 aatgttaaga aatgggtttc ttgccttaac cagtctctca agtgatgaga cagtgaagta 2821 aaattgagtg cactaaacaa ataagattct gaggaagtct tatcttctgc agtgagtatg 2881 gcccgatgct ttctgtggct aaacagatgt aatgggaaga aataaaagcc tacgtgttgg 2941 taaatccaac agcaagggag atttttgaat cataataact cataaggtgc tatctgttca 3001 gtgatgccct cagagctctt gctgttagct ggcagctgac gctgctagga tagttagttt 3061 ggaaatggta cttcataata aactacacaa ggaaagtcag ccactgtgtc ttatgaggaa 3121 ttggacctaa taaattttag tgtgccttcc aaacctgaga atatatgctt ttggaagtta 3181 aaatttaaat ggcttttgcc acatacatag atcttcatga tgtgtgagtg taattccatg 3241 tggatatcag ttaccaaaca ttacaaaaaa attttatggc ccaaaatgac caacgaaatt 3301 gttacaatag aatttatcca attttgatct ttttatattc ttctaccaca cctggaaaca 3361 gaccaataga cattttgggg ttttataata ggaatttgta taaagcatta ctctttttca 3421 ataaattgtt ttttaattta aaaaaaggat ta

An exemplary human CLDN2 amino acid sequence is set forth below (SEQ ID NO: 39; GenBank Accession No: AAH71747.1, Version 1, incorporated herein by reference):

  1 maslglqlvg yilgllgllg tlvamllpsw ktssyvgasi vtavgfskgl wmecathstg  61 itqcdiystl lglpadigaa qammvtssai sslaciisvv gmrctvfcge srakdrvava 121 ggvffilggl lgfipvawnl hgilrdfysp lvpdsmkfei gealylgiis slfsliagii 181 lcfscssqrn rsnyydayqa qplatrsspr pgqppkvkse fnsysltgyv

An exemplary human CLDN2 nucleic acid sequence is set forth below (SEQ ID NO: 40; GenBank Accession No: NM_020384.3, Version 3, incorporated herein by reference):

   1 aagtctctga cccacggctc agatttgcag atggattttg caaagctgtg gttaacgatt   61 agaaatcctt tatcacctca gcccgtggcc ccttgtactt cgctcccctc cctcaggatc  121 cctttctccc tctccagggg catctccccc tccaaggctc tgcaaagaac tgccctgtct  181 tctagatgcc ttcttgaggc tgcttgtggc cacccacaga cacttgtaag gaggagagaa  241 gtcagcctgg cagagagact ctgaaatgag ggattagagg tgttcaagga gcaagagctt  301 cagcctgaag acaagggagc agtccctgaa gacgcttcta ctgagaggtc tgccatggcc  361 tctcttggcc tccaacttgt gggctacatc ctaggccttc tggggctttt gggcacactg  421 gttgccatgc tgctccccag ctggaaaaca agttcttatg tcggtgccag cattgtgaca  481 gcagttggct tctccaaggg cctctggatg gaatgtgcca cacacagcac aggcatcacc  541 cagtgtgaca tctatagcac ccttctgggc ctgcccgctg acatccaggc tgcccaggcc  601 atgatggtga catccagtgc aatctcctcc ctggcctgca ttatctctgt ggtgggcatg  661 agatgcacag tcttctgcca ggaatcccga gccaaagaca gagtggcggt agcaggtgga  721 gtctttttca tccttggagg cctcctggga ttcattcctg ttgcctggaa tcttcatggg  781 atcctacggg acttctactc accactggtg cctgacagca tgaaatttga gattggagag  841 gctctttact tgggcattat ttcttccctg ttctccctga tagctggaat catcctctgc  901 ttttcctgct catcccagag aaatcgctcc aactactacg atgcctacca agcccaacct  961 cttgccacaa ggagctctcc aaggcctggt caacctccca aagtcaagag tgagttcaat 1021 tcctacagcc tgacagggta tgtgtgaaga accaggggcc agagctgggg ggtggctggg 1081 tctgtgaaaa acagtggaca gcaccccgag ggccacaggt gagggacact accactggat 1141 cgtgtcagaa ggtgctgctg aggatagact gactttggcc attggattga gcaaaggcag 1201 aaatgggggc tagtgtaaca gcatgcaggt tgaattgcca aggatgctcg ccatgccagc 1261 ctttctgttt tcctcacctt gctgctcccc tgccctaagt ccccaaccct caacttgaaa 1321 ccccattccc ttaagccagg actcagagga tccctttgcc ctctggttta cctgggactc 1381 catccccaaa cccactaatc acatcccact gactgaccct ctgtgatcaa agaccctctc 1441 tctggctgag gttggctctt agctcattgc tggggatggg aaggagaagc agtggctttt 1501 gtgggcattg ctctaaccta cttctcaagc ttccctccaa agaaactgat tggccctgga 1561 acctccatcc cactcttgtt atgactccac agtgtccaga ctaatttgtg catgaactga 1621 aataaaacca tcctacggta tccagggaac agaaagcagg atgcaggatg ggaggacagg 1681 aaggcagcct gggacattta aaaaaataaa aatgaaaaaa aaacccagaa cccatttctc 1741 agggcacttt ccagaattct ctcatatttg tgggctggga tcaagcctgc agcttgagga 1801 aagcacaagg aaaggaaaga agatctggtg gaaagctcag gtggcagcgg actctgactc 1861 cactgaggaa ctgcctcaga agctgcgatc acaactttgg ctgaagcccc tgcctcactc 1921 tagggcacct gacctggcct cttgcctaaa ccacaaggct aagggctata gacaatggtt 1981 tccttaggaa cagtaaacca gtttttctag ggatggccct tggctggggg atgacagtgt 2041 gggagctgtg gggtactgag gaagacacca ttccttgacg gtgtctaaga agccaggtgg 2101 atgtgtgtgg tggctccagt gggtgtttct actctgccag tgagaggcag ccccctagaa 2161 actcttcagg cgtaatggaa aatcagctca aatgagatca ggccccccca gggtccaccc 2221 acagagcact acagagcctc tgaaagacca tagcaccaag cgagcccctt cagattcccc 2281 cactgtccat cggaagatgc tccagagtgg ctagagggca tctaagggct ccagcatggc 2341 atatccatgc ccacggtgct gtgtccatga tctgagtgat agctgcactg ctgcctggga 2401 ttgcagctga ggtgggagtg gagaatggtt cccaggaaga cagttccacc tctaaggtcc 2461 gaaaatgttc cctttaccct ggagtgggag tgaggggtca tacaccaaag gtattttccc 2521 tcaccagtct aggcatgact ggcttctgaa aaattccagc acacctcctc gaacctcatt 2581 gtcagcagag agggcccatc tgttgtctgt aacatgcctt tcacatgtcc accttcttgc 2641 catgttccag ctgctctccc aacctggaag gccgtctccc cttagccaag tcctcctcag 2701 gcttggagaa cttcctcagc gtcacctcct tcattgagcc ttctctgatc actccatccc 2761 tctcctaccc ctccctcccc caaccctcaa tgtataaatt gcttcttgat gcttagcatt 2821 cacaattttt gattgatcgt tatttgtgtg tgtgtgtccg atctcacaag tatattgtaa 2881 acccttcggt gggtgggggc catatcctag acctctctgt atcccccaga ctatctgtaa 2941 cagtgccagg cacacagtag gtgatcaata aacacttgtt gattgagaaa aaaaaaaa

An exemplary human EYA1 amino acid sequence is set forth below (SEQ ID NO: 41; GenBank Accession No: AAI21799.1, Version 1, incorporated herein by reference):

  1 mfpsnawafy flsfltnsrp yphilptpss qtmaaygqtq fttgmqqata yatypqpgqp  61 ygissygalw agikteggls qsqspgqtgf lsygtsfstp qpgqapysyq mqgssfttss 121 giytgnnslt nssgfnssqq dypsypsfgq gqyaqyynss pypahymtss ntspttpstn 181 atyqlqepps gitsqavtdp taeystihsp stpikdsdsd rlrrgsdgks rgrgrrnnnp 241 spppdsdler vfiwdldeti ivfhslltgs yanrygrdpp tsyslglrme emifnladth 301 lffndleecd qvhiddvssd dngqdlstyn fgtdgfpaaa tsanlclatg vrggvdwmrk 361 lafryrrvke iyntyknnvg gllgpakrea wlqlraeiea ltdswltlal kalslihsrt 421 ncvnilvttt qlipalakvl lyglgivfpi eniysatkig kescferiiq rfgrkvvyvv 481 igdgveeeqg akkhampfwr isshsdlmal hhaleleyl

An exemplary human EYA1 nucleic acid sequence is set forth below (SEQ ID NO: 42; GenBank Accession No: NM_001288574.1, Version 1, incorporated herein by reference):

   1 aaaccaataa ggttaggaca agagaatagc tgtggtttgc gttgcaaaaa ccaaaaaaaa   61 aaaaaaaaaa aaaaaaagaa agccccgagg ctccatgggc agacctacaa ggctgcgcaa  121 acaaatcgag ggatgagatt ctgctgtttc tttgtctagg gttctcagat gctatctgcc  181 gctgctgttt ggtggggaag gagcgctggg cgcaaagctg ttaccaaaca gaacggtggg  241 agctgatggc tccgagtttg gggcgaggta gaaactctcc agtgccactt ccgactttaa  301 gccttcctgt tgccgtccac tgtggcgggt ttcttcctgg ggaacacgtt ttcgctcagt  361 cgctcggcag cccgagcctg cggcagcggc caggcgcctg ccccctgcgc cgagctttcc  421 cctgcagagg cgctccactc ccagaagcgc cgcggctgca ccagagcgcc tgagagcccc  481 cgcgcgtacc catccaggag caaaactatg tcaggaatgg aggtttgcta acccagaaaa  541 ttcgaaggaa cacattaaac tggtggatgc agcagatgta agcgctgtgc aaacatctca  601 agccagttca gatgttgctg tttcctcaag ttgcaggtct atggaaatgc aggatctaac  661 cagcccgcat agccgtctga gtggtagtag tgaatccccc agtggcccca aactcggtaa  721 ctctcatata aatagtaatt ccatgactcc caatggcacc gaagttaaaa cagagccaat  781 gagcagcagt gaaacagctt caacgacagc cgacgggtct ttaaacaatt tctcaggttc  841 agcaattggg agcagtagtt tcagcccacg accaactcac cagttctctc caccacagat  901 ttacccttcc aaaccatacc cacatattct ccctacccct tcctcacaaa ctatggctgc  961 atatgggcaa acacagttta ccacaggaat gcaacaagct acagcctatg ccacgtaccc 1021 acagccagga cagccgtacg gcatttcctc atatggcatc aagactgaag gtggattgtc 1081 acagtctcag tcacctggac agacaggatt tctcagctat ggcacaagct tcagtacccc 1141 tcaacctgga caggcaccat acagctacca gatgcaaggt agcagtttta caacatcatc 1201 aggaatatat acaggaaata attcactcac aaattcctct ggatttaata gttcacagca 1261 ggactatccg tcttatccca gttttggcca gggtcagtac gcacagtatt ataacagctc 1321 accgtatcca gcacattata tgaccagcag caacaccagc ccaacgacac catccaccaa 1381 tgccacttac cagcttcaag aaccgccatc tggcatcacc agccaagcag ttacagatcc 1441 cacagcagag tacagcacaa tccacagccc atcaacaccc attaaagatt cagattctga 1501 tcgattgcgt cgaggttcag atgggaaatc acgtggacgg ggccgaagaa acaataatcc 1561 ttcacctccc ccagattctg atcttgagag agtgttcatc tgggacttgg atgagacaat 1621 cattgttttc cactccttgc ttactgggtc ctacgccaac agatatggga gggatccacc 1681 cacttcagtt tcccttggac tgcgaatgga agaaatgatt ttcaacttgg cagacacaca 1741 tttatttttt aatgacttag aagaatgtga ccaagtccat atagatgatg tttcttcaga 1801 tgataacgga caggacctaa gcacatataa ctttggaaca gatggctttc ctgctgcagc 1861 aaccagtgct aacttatgtt tggcaactgg tgtacggggc ggtgtggact ggatgagaaa 1921 gttggccttc cgctacagac gggtaaaaga gatctacaac acctacaaaa ataatgttgg 1981 aggtctgctt ggtccagcta agagggaagc ctggctgcag ttgagggccg aaattgaagc 2041 cctgaccgac tcctggttga cactggccct gaaagcactc tcgctcattc actcccggac 2101 aaactgtgtg aatattttag taacaactac tcagctcatc ccagcattgg cgaaagtcct 2161 gctgtatggg ttaggaattg tatttccaat agaaaatatt tacagtgcaa ctaaaatagg 2221 aaaagaaagc tgttttgaga gaataattca aaggtttgga agaaaagtgg tgtatgttgt 2281 tataggagat ggtgtagaag aagaacaagg agcaaaaaag cacgcgatgc ccttctggag 2341 gatctccagc cactcggacc tcatggccct gcaccatgcc ttggaactgg agtacctgta 2401 acagcgctcg gcactttgac agcgcacagc tgctctgtga ccagggacag atccagcagg 2461 ccccagtctc gcatcagcgc cggcctccag aacttagcaa tttccgcctg gtgatgcgca 2521 gttgctgtca gtcttgacct ctgcctttgt ggtgaatgga ggaccacgtc tatttcatca 2581 gaacagctgt tgactctagt actgtgaatc cagtgaaaat aagccatgag aatgttttag 2641 cacagcgtta tgtgtctgcc acattaacta cacggttcaa acctgtgaag aaaggacctg 2701 caaacgcttc agttgttagc attttcaatg tgatataaac agcttctcca atacagcaaa 2761 cctaattgca caacagagac tgaaatgtgt ttcctgaata ccagtggagg aattttcttg 2821 taaagaaggt ttactttttg gtgtctcata cccagggtaa tctgtacatc tctacttatt 2881 tatgaacaga ctttttttaa aaagataaaa aaacagcttt attgaggtat aattcaccca 2941 ccagactttt ttaaacatca aataattgaa gagacaatag cattagaaat aagtgattaa 3001 aggcctctgc ctcacaacat ggcaagtaca gtactttgaa ttttagcaca ttgcatagta 3061 gttttaagta tgtctaattt aaacgtataa tatgtacatc actgagacaa tcatgtacag 3121 aaagaatttt tggtgtaaat ttgtaataat ggataattct tttacatatt gtttagggaa 3181 atgatattga aaggtagcaa tgcctggata gtgaagcatg aggcagcacg tgcacaaatt 3241 catgtgccgt gccttatctg agttttcggt ataaatatgt agataatgga tttttttttt 3301 ttagataatg ttgtcaagac caaaagcatg gatgtcaagt gtcagtaagg attttgtttt 3361 ctaaaatttt ttcctgcatc agttcttctg agggccttga tgaaataaca cagcagtttc 3421 ttaaacaatt tgaaacaaaa tgagctctcc taccacctca ctttttcatt tccacactaa 3481 tgtattatat gtaactactt ggaaaaaata attattcaaa tgcttcttcc cacaaagaat 3541 atagatgata gtagatatat tttattaata aaatggttca tgaatcggag actaacaaag 3601 ttttcatgtg ctcagaatta ttaattatcg tgtctgcatt ttctttcgat aaaggaagac 3661 acacgatgct aatccggaaa tcagcaaact ttgcattact ccctatgtgc gtattttctc 3721 tttcttcctg tcaccctgag gaaggttcat tgccattgtc atcaccatgg aaacaacgtt 3781 cctctccacc tgcattatgt actacatgac aggcatcaat ctggggaaat aataaaatta 3841 tcacctttgt cagaccataa gagtttctcc aaaagtggtc agtttggctg ggcaatattt 3901 tctctcatct aacaaacaca atccattgtc atgaaattac ccttaggatg agtcttcttt 3961 aatcaatcat atattgggcg gaaaaaacac cagctttgac ccgaagtagt tgaagagcta 4021 cttcattctt ttctgaagtt gtgtgttgct gctagaaata gtcatttgtg aattatccaa 4081 attgtttaaa ttcacaattg aattagtttt ttcttccttt ttgcttgaag caaacagttg 4141 acaattttta accttttcat tttatgtttt tgtactctgc agactgaaaa gacaaagttt 4201 atcttggcct tactgtataa aggtgtgctg tgtccaccgt tgtgtacaga atttttcttc 4261 attaattttg tgtttaagtt aataaaattt atttgtgatg tactgtaaaa aaaaaaaaaa 4321 aaa

An exemplary human SNAI1 amino acid sequence is set forth below (SEQ ID NO: 43; GenBank Accession No: CAB52414.1, Version 1, incorporated herein by reference):

  1 mprsflvrkp sdpnrkpnys elqdsnpeft fqqpydqahl laaipppeil nptaslpmli  61 wdsvlapqaq piawaslrlq esprvaelts lsdedsgkgs qppsppspap ssfsstsvss 121 leaeayaafp glgqvpkqla qlseakdlqa rkafnckycn keylslgalk mhirshtlpc 181 vcgtcgkafs rpwllqghvr thtgekpfsc phcsrafadr snlrahlqth sdvkkyqcqa 241 cartfsrmsl lhkhqesgcs gcpr

An exemplary human SNAI1 nucleic acid sequence is set forth below (SEQ ID NO: 44; GenBank Accession No: NM_005985.3, Version 3, incorporated herein by reference):

   1 attcattgcg ccgcggcacg gcctagcgag tggttcttct gcgctactgc tgcgcgaatc   61 ggcgacccca gtgcctcgac cactatgccg cgctctttcc tcgtcaggaa gccctccgac  121 cccaatcgga agcctaacta cagcgagctg caggactcta atccagagtt taccttccag  181 cagccctacg accaggccca cctgctggca gccatcccac ctccggagat cctcaacccc  241 accgcctcgc tgccaatgct catctgggac tctgtcctgg cgccccaagc ccagccaatt  301 gcctgggcct cccttcggct ccaggagagt cccagggtgg cagagctgac ctccctgtca  361 gatgaggaca gtgggaaagg ctcccagccc cccagcccac cctcaccggc tccttcgtcc  421 ttctcctcta cttcagtctc ttccttggag gccgaggcct atgctgcctt cccaggcttg  481 ggccaagtgc ccaagcagct ggcccagctc tctgaggcca aggatctcca ggctcgaaag  541 gccttcaact gcaaatactg caacaaggaa tacctcagcc tgggtgccct caagatgcac  601 atccgaagcc acacgctgcc ctgcgtctgc ggaacctgcg ggaaggcctt ctctaggccc  661 tggctgctac aaggccatgt ccggacccac actggcgaga agcccttctc ctgtccccac  721 tgcagccgtg ccttcgctga ccgctccaac ctgcgggccc acctccagac ccactcagat  781 gtcaagaagt accagtgcca ggcgtgtgct cggaccttct cccgaatgtc cctgctccac  841 aagcaccaag agtccggctg ctcaggatgt ccccgctgac cctcgaggct ccctcttcct  901 ctccatacct gcccctgcct gacagccttc cccagctcca gcaggaagga ccccacatcc  961 ttctcactgc catggaattc cctcctgagt gccccacttc tggccacatc agccccacag 1021 gactttgatg aagaccattt tctggttctg tgtcctctgc ctgggctctg gaagaggcct 1081 tcccatggcc atttctgtgg agggagggca gctggccccc agccctgggg gattcctgag 1141 ctggcctgtc tgcgtgggtt tttgtatcca gagctgtttg gatacagctg ctttgagcta 1201 caggacaaag gctgacagac tcactgggaa gctcccaccc cactcagggg accccactcc 1261 cctcacacac acccccccac aaggaaccct caggccaccc tccacgaggt gtgactaact 1321 atgcaataat ccacccccag gtgcagcccc agggcctgcg gaggcggtgg cagactagag 1381 tctgagatgc cccgagccca ggcagctatt tcagcctcct gtttggtggg gtggcacctg 1441 tttcccgggc aatttaacaa tgtctgaaaa gggactgtga gtaatggctg tcacttgtcg 1501 ggggcccaag tggggtgctc tggtctgacc gatgtgtctc ccagaactat tctgggggcc 1561 cgacaggtgg gcctgggagg aagatgttta catttttaaa ggtacactgg tatttatatt 1621 tcaaacattt tgtatcaagg aaacgttttg tatagttata tgtacagttt attgatattc 1681 aataaagcag ttaatttata tattaaaaaa aaaaaaaaaa aa

An exemplary human TGFB2 amino acid sequence is set forth below (SEQ ID NO: 45; GenBank Accession No: AAH99635.1, Version 1, incorporated herein by reference):

  1 mhycvlsafl ilhlvtvals lstcstldmd qfmrkrieai rgqilsklkl tsppedypep  61 eevppevisi ynstrdllqe kasrraaace rersdeeyya kevykidmpp ffpsenaipp 121 tfyrpyfriv rfdvsamekn asnlvkaefr vfrlqnpkar vpeqrielyq ilkskdltsp 181 tqryidskvv ktraegewls fdvtdavhew lhhkdrnlgf kislhcpcct fvpsnnyiip 241 nkseelearf agidgtstyt sgdqktikst rkknsgktph lllmllpsyr lesqqtnrrk 301 kraldaaycf rnvgdncclr plyidfkrdl gwkwihepkg ynanfcagac pylwssdtqh 361 srvlslynti npeasaspcc vsqdleplti lyyigktpki eqlsnmivks ckcs

An exemplary human TGFB2 nucleic acid sequence is set forth below (SEQ ID NO: 46; GenBank Accession No: NM_001135599.3, Version 3, incorporated herein by reference):

   1 agacacgtgg ttcagagaga acttataaat ctcccctccc cggcaagatc gtgatgttat   61 ctgctggcag cagaaggttc gctccgagcg gagctccaga agctcctgac aagagaaaga  121 cagattgaga tagagataga aagagaaaga gagaaagaga cagcagagcg agagcgcaag  181 tgaaagaggc aggggagggg gatggagaat attagcctga cggtctaggg agtcatccag  241 gaacaaactg aggggctgcc cggctgcaga caggaggaga cagagaggat ctattttagg  301 gtggcaagtg cctacctacc ctaagcgagc aattccacgt tggggagaag ccagcagagg  361 ttgggaaagg gtgggagtcc aagggagccc ctgcgcaacc ccctcaggaa taaaactccc  421 cagccagggt gtcgcaaggg ctgccgttgt gatccgcagg gggtgaacgc aaccgcgacg  481 gctgatcgtc tgtggctggg ttggcgtttg gagcaagaga aggaggagca ggagaaggag  541 ggagctggag gctggaagcg tttgcaagcg gcggcggcag caacgtggag taaccaagcg  601 ggtcagcgcg cgcccgccag ggtgtaggcc acggcgcgca gctcccagag caggatccgc  661 gccgcctcag cagcctctgc ggcccctgcg gcacccgacc gagtaccgag cgccctgcga  721 agcgcaccct cctccccgcg gtgcgctggg ctcgccccca gcgcgcgcac acgcacacac  781 acacacacac acacacacgc acgcacacac gtgtgcgctt ctctgctccg gagctgctgc  841 tgctcctgct ctcagcgccg cagtggaagg caggaccgaa ccgctccttc tttaaatata  901 taaatttcag cccaggtcag cctcggcggc ccccctcacc gcgctcccgg cgcccctccc  961 gtcagttcgc cagctgccag ccccgggacc ttttcatctc ttcccttttg gccggaggag 1021 ccgagttcag atccgccact ccgcacccga gactgacaca ctgaactcca cttcctcctc 1081 ttaaatttat ttctacttaa tagccactcg tctctttttt tccccatctc attgctccaa 1141 gaattttttt cttcttactc gccaaagtca gggttccctc tgcccgtccc gtattaatat 1201 ttccactttt ggaactactg gccttttctt tttaaaggaa ttcaagcagg atacgttttt 1261 ctgttgggca ttgactagat tgtttgcaaa agtttcgcat caaaaacaac aacaacaaaa 1321 aaccaaacaa ctctccttga tctatacttt gagaattgtt gatttctttt ttttattctg 1381 acttttaaaa acaacttttt tttccacttt tttaaaaaat gcactactgt gtgctgagcg 1441 cttttctgat cctgcatctg gtcacggtcg cgctcagcct gtctacctgc agcacactcg 1501 atatggacca gttcatgcgc aagaggatcg aggcgatccg cgggcagatc ctgagcaagc 1561 tgaagctcac cagtccccca gaagactatc ctgagcccga ggaagtcccc ccggaggtga 1621 tttccatcta caacagcacc agggacttgc tccaggagaa ggcgagccgg agggcggccg 1681 cctgcgagcg cgagaggagc gacgaagagt actacgccaa ggaggtttac aaaatagaca 1741 tgccgccctt cttcccctcc gaaactgtct gcccagttgt tacaacaccc tctggctcag 1801 tgggcagctt gtgctccaga cagtcccagg tgctctgtgg gtaccttgat gccatcccgc 1861 ccactttcta cagaccctac ttcagaattg ttcgatttga cgtctcagca atggagaaga 1921 atgcttccaa tttggtgaaa gcagagttca gagtctttcg tttgcagaac ccaaaagcca 1981 gagtgcctga acaacggatt gagctatatc agattctcaa gtccaaagat ttaacatctc 2041 caacccagcg ctacatcgac agcaaagttg tgaaaacaag agcagaaggc gaatggctct 2101 ccttcgatgt aactgatgct gttcatgaat ggcttcacca taaagacagg aacctgggat 2161 ttaaaataag cttacactgt ccctgctgca cttttgtacc atctaataat tacatcatcc 2221 caaataaaag tgaagaacta gaagcaagat ttgcaggtat tgatggcacc tccacatata 2281 ccagtggtga tcagaaaact ataaagtcca ctaggaaaaa aaacagtggg aagaccccac 2341 atctcctgct aatgttattg ccctcctaca gacttgagtc acaacagacc aaccggcgga 2401 agaagcgtgc tttggatgcg gcctattgct ttagaaatgt gcaggataat tgctgcctac 2461 gtccacttta cattgatttc aagagggatc tagggtggaa atggatacac gaacccaaag 2521 ggtacaatgc caacttctgt gctggagcat gcccgtattt atggagttca gacactcagc 2581 acagcagggt cctgagctta tataatacca taaatccaga agcatctgct tctccttgct 2641 gcgtgtccca agatttagaa cctctaacca ttctctacta cattggcaaa acacccaaga 2701 ttgaacagct ttctaatatg attgtaaagt cttgcaaatg cagctaaaat tcttggaaaa 2761 gtggcaagac caaaatgaca atgatgatga taatgatgat gacgacgaca acgatgatgc 2821 ttgtaacaag aaaacataag agagccttgg ttcatcagtg ttaaaaaatt tttgaaaagg 2881 cggtactagt tcagacactt tggaagtttg tgttctgttt gttaaaactg gcatctgaca 2941 caaaaaaagt tgaaggcctt attctacatt tcacctactt tgtaagtgag agagacaaga 3001 agcaaatttt ttttaaagaa aaaaataaac actggaagaa tttattagtg ttaattatgt 3061 gaacaacgac aacaacaaca acaacaacaa acaggaaaat cccattaagt ggagttgctg 3121 tacgtaccgt tcctatcccg cgcctcactt gatttttctg tattgctatg caataggcac 3181 ccttcccatt cttactctta gagttaacag tgagttattt attgtgtgtt actatataat 3241 gaacgtttca ttgcccttgg aaaataaaac aggtgtataa agtggagacc aaatactttg 3301 ccagaaactc atggatggct taaggaactt gaactcaaac gagccagaaa aaaagaggtc 3361 atattaatgg gatgaaaacc caagtgagtt attatatgac cgagaaagtc tgcattaaga 3421 taaagaccct gaaaacacat gttatgtatc agctgcctaa ggaagcttct tgtaaggtcc 3481 aaaaactaaa aagactgtta ataaaagaaa ctttcagtca gaataagtct gtaagttttt 3541 ttttttcttt ttaattgtaa atggttcttt gtcagtttag taaaccagtg aaatgttgaa 3601 atgttttgac atgtactggt caaacttcag accttaaaat attgctgtat agctatgcta 3661 taggtttttt cctttgtttt ggtatatgta accataccta tattattaaa atagatggat 3721 atagaagcca gcataattga aaacacatct gcagatctct tttgcaaact attaaatcaa 3781 aacattaact actttatgtg taatgtgtaa atttttacca tattttttat attctgtaat 3841 aatgtcaact atgatttaga ttgacttaaa tttgggctct ttttaatgat cactcacaaa 3901 tgtatgtttc ttttagctgg ccagtacttt tgagtaaagc ccctatagtt tgacttgcac 3961 tacaaatgca tttttttttt aataacattt gccctacttg tgctttgtgt ttctttcatt 4021 attatgacat aagctacctg ggtccacttg tcttttcttt tttttgtttc acagaaaaga 4081 tgggttcgag ttcagtggtc ttcatcttcc aagcatcatt actaaccaag tcagacgtta 4141 acaaattttt atgttaggaa aaggaggaat gttatagata catagaaaat tgaagtaaaa 4201 tgttttcatt ttagcaagga tttagggttc taactaaaac tcagaatctt tattgagtta 4261 agaaaagttt ctctaccttg gtttaatcaa tatttttgta aaatcctatt gttattacaa 4321 agaggacact tcataggaaa catctttttc tttagtcagg tttttaatat tcagggggaa 4381 attgaaagat atatatttta gtcgattttt caaaagggga aaaaagtcca ggtcagcata 4441 agtcattttg tgtatttcac tgaagttata aggtttttat aaatgttctt tgaaggggaa 4501 aaggcacaag ccaatttttc ctatgatcaa aaaattcttt ctttcctctg agtgagagtt 4561 atctatatct gaggctaaag tttaccttgc tttaataaat aatttgccac atcattgcag 4621 aagaggtatc ctcatgctgg ggttaataga atatgtcagt ttatcacttg tcgcttattt 4681 agctttaaaa taaaaattaa taggcaaagc aatggaatat ttgcagtttc acctaaagag 4741 cagcataagg aggcgggaat ccaaagtgaa gttgtttgat atggtctact tcttttttgg 4801 aatttcctga ccattaatta aagaattgga tttgcaagtt tgaaaactgg aaaagcaaga 4861 gatgggatgc cataatagta aacagccctt gtgttggatg taacccaatc ccagatttga 4921 gtgtgtgttg attatttttt tgtcttccac ttttctatta tgtgtaaatc acttttattt 4981 ctgcagacat tttcctctca gataggatga cattttgttt tgtattattt tgtctttcct 5041 catgaatgca ctgataatat tttaaatgct ctattttaag atctcttgaa tctgtttttt 5101 ttttttttaa tttgggggtt ctgtaaggtc tttatttccc ataagtaaat attgccatgg 5161 gaggggggtg gaggtggcaa ggaaggggtg aagtgctagt atgcaagtgg gcagcaatta 5221 tttttgtgtt aatcagcagt acaatttgat cgttggcatg gttaaaaaat ggaatataag 5281 attagctgtt ttgtattttg atgaccaatt acgctgtatt ttaacacgat gtatgtctgt 5341 ttttgtggtg ctctagtggt aaataaatta tttcgatgat atgtggatgt ctttttccta 5401 tcagtaccat catcgagtct agaaaacacc tgtgatgcaa taagactatc tcaagctgga 5461 aaagtcatac cacctttccg attgccctct gtgctttctc ccttaaggac agtcacttca 5521 gaagtcatgc tttaaagcac aagagtcagg ccatatccat caaggataga agaaatccct 5581 gtgccgtctt tttattccct tatttattgc tatttggtaa ttgtttgaga tttagtttcc 5641 atccagcttg actgccgacc agaaaaaatg cagagagatg tttgcaccat gctttggctt 5701 tctggttcta tgttctgcca acgccagggc caaaagaact ggtctagaca gtatcccctg 5761 tagccccata acttggatag ttgctgagcc agccagatat aacaagagcc acgtgctttc 5821 tggggttggt tgtttgggat cagctacttg cctgtcagtt tcactggtac cactgcacca 5881 caaacaaaaa aacccaccct atttcctcca atttttttgg ctgctaccta caagaccaga 5941 ctcctcaaac gagttgccaa tctcttaata aataggatta ataaaaaaag taattgtgac 6001 tcaaaaaaaa aaaaaa

An exemplary human WNT3 amino acid sequence is set forth below (SEQ ID NO: 47; GenBank Accession No: BAB70502.1, Version 1, incorporated herein by reference):

  1 mephllglll glllggtrvl agypiwwsla lgqqytslgs qpllcgsipg lvpkqlrfcr  61 nyieimpsva egvklgiqec qhqfrgrrwn cttiddslai fgpvldkatr esafvhaias 121 agvafavtrs caegtsticg cdshhkgppg egwkwggcse dadfgvlvsr efadarenrp 181 darsamnkhn neagrttild hmhlkckchg lsgscevktc wwaqpdfrai gdflkdkyds 241 asemvvekhr esrgwvetlr akyslfkppt erdlvyyens pnfcepnpet gsfgtrdrtc 301 nvtshgidgc dllccgrghn trtekrkekc hcifhwccyv scqeciriyd vhtck

An exemplary human WNT3 nucleic acid sequence is set forth below (SEQ ID NO: 48; GenBank Accession No: NM_030753.4, Version 4, incorporated herein by reference):

   1 tgctccgcgc tgggctcggg aggggggcgg ctgcgggtgg aggtgcgctt ctgacaagcc   61 cgaaagtcat ttccaatctc aagtggactt tgttccaact attgggggcg tcgctccccc  121 tcttcatggt cgcgggcaaa cttcctcctc ggcgcctctt ctaatggagc cccacctgct  181 cgggctgctc ctcggcctcc tgctcggtgg caccagggtc ctcgctggct acccaatttg  241 gtggtccctg gccctgggcc agcagtacac atctctgggc tcacagcccc tgctctgcgg  301 ctccatccca ggcctggtcc ccaagcaact gcgcttctgc cgcaattaca tcgagatcat  361 gcccagcgtg gccgagggcg tgaagctggg catccaggag tgccagcacc agttccgggg  421 ccgccgctgg aactgcacca ccatagatga cagcctggcc atctttgggc ccgtcctcga  481 caaagccacc cgcgagtcgg ccttcgttca cgccatcgcc tcggccggcg tggccttcgc  541 cgtcacccgc tcctgcgccg agggcacctc caccatttgc ggctgtgact cgcatcataa  601 ggggccgcct ggcgaaggct ggaagtgggg cggctgcagc gaggacgctg acttcggcgt  661 gttagtgtcc agggagttcg cggatgcgcg cgagaacagg ccggacgcgc gctcggccat  721 gaacaagcac aacaacgagg cgggccgcac gactatcctg gaccacatgc acctcaaatg  781 caagtgccac gggctgtcgg gcagctgtga ggtgaagacc tgctggtggg cgcagcctga  841 cttccgtgcc atcggtgact tcctcaagga caagtatgac agcgcctcgg agatggtagt  901 agagaagcac cgtgagtccc gaggctgggt ggagaccctc cgggccaagt actcgctctt  961 caagccaccc acggagaggg acctggtcta ctacgagaac tcccccaact tttgtgagcc 1021 caacccagag acgggttcct ttggcacaag ggaccggact tgcaatgtca cctcccacgg 1081 catcgatggc tgcgatctgc tctgctgtgg ccggggccac aacacgagga cggagaagcg 1141 gaaggaaaaa tgccactgca tcttccactg gtgctgctac gtcagctgcc aggagtgtat 1201 tcgcatctac gacgtgcaca cctgcaagta gggcaccagg gcgctgggaa ggggtgaagt 1261 gtgtggctgg gcggattcag cgaagtctca tgggaagcag gacctagagc cgggcacagc 1321 cctcagcgtc agacagcaag gaactgtcac cagccgcacg cgtggtaaat gacccagacc 1381 caactcgcct gtggacgggg aggctctccc tctctctcat cttacatttc tcaccctact 1441 ctggatggtg tgtggttttt aaagaagggg gctttctttt tagttctcta gggtctgata 1501 ggaacagacc tgaggcttat ctttgcacat gttaaagaaa ataaaaatga aaaaaaattt 1561 gactccaaca gaacaggctg ggctaatgtg agctctcagc ctggcagtca agacatcagc 1621 atgggcaagg ttctgtttcc aaactgctgc ttctggtgac attccaagac gcctggaggg 1681 tgggagtcag gaagtaggac acacccctgc agtctccttt tcttggtcca ctcccattca 1741 aatttgagct aatttctcat tctgataaaa gccataggtt tagctaggat gaagtggtag 1801 gaaggtccgt ggcagttgtt agagtaggat ttggagtttg gaagaactgg cagctcaggg 1861 tggcctggtc agccgtttga agagcagcca tgtgttcttc tcagtctcat tttctctata 1921 accctgttct gcacgagggg cagtcagatc tcaaaatctt tttctaccat tctgcagttt 1981 ccaccgtcaa tgcagttttt tttttgtttt tttgtttttt tttttttttg gtggtagtgg 2041 accttgtaaa taggctatgt aagggggcaa gtcttctcta gctcaaatgg cttcctaaat 2101 aaataagcgg tatcttcaga aggggccatt cagtccttcc cagccctgct cacctgcaga 2161 ttctctgtac aaataactcc aggtagagca gttggactcc aggtcacctt agtataagtt 2221 agacaaaggg tccgtgaggg agtagccatc aattcctgaa attccaactt tgtgactagc 2281 agatggggag gatgaaaacc atccctttgc ttcctctcca atacggaccc atcttactgt 2341 gtcctttcct ctctggggcc aatgtgagta aacacagaca cagagttctt tcccccagct 2401 cttcctccct cacctgcatg ctgagatagc ttccatccat gcagttccca aggatctgga 2461 ttagaagttc aaaggggaac cagcagtcac ctactccctt aggtgaagca tctcacggct 2521 gagttctccc tgaggcatac tggtccagct gagcgtccta gagaaagcta gcaaaaggga 2581 ggcacatgga tttcacagta tgaattggtt caacaactgt cttagggaga atcagaaaga 2641 agagatgcag caggggaatg agcagaacaa agatttttct ttctccccct tctctctggg 2701 gtctacctaa ccctgaccta aaataccagg gcagcgatct cccagctggt gcaggtgggc 2761 ttgccaagat ggtcgtccag gagcccgcct tcacttctaa atctgctggc cacaagccct 2821 gctaaagata cacatctcac cccctccgcc aagtctgaaa tgcccctccc catctcacct 2881 tagactgaaa agttttaaat catgtcaact ggataatact tgctttatgt gagaatactt 2941 cagcagaatg gatacgaatt ttcaaaacaa tcttttcata tctatgtatt ctatattaaa 3001 agtgataaag tcatgtttct ggggcgtatt caagtagctg acaagtaatt atttaataat 3061 agtacatgag tgcattgtaa tgattctcgc cgtagtcagg taatagtatc caaccgaaat 3121 ttcctaccaa cctgctgtat ccaaagtttt gtaaaaagtt gtagaagttg ttgatctttt 3181 tgattttata ttcaaaaagt ctctttttat aaatattatt tattatacaa tgtatatacc 3241 tttgagttaa ctaagattat atattatata aatatatata tatttggaga aaatatattt 3301 catcatgcag tttttttctg ttaagtcatt aaagagaagg taaacaaacc taaaaaaaaa 3361 aaaaaaaaaa aaaaaaaaaa aaaaa

An exemplary human HOXD13 amino acid sequence is set forth below (SEQ ID NO: 49; GenBank Accession No: AAC51635.1, Version 1, incorporated herein by reference):

  1 mdglradggg aggapassss ssvaaaaasg qcrgflsapv fagthsgraa aaaaaaaaaa  61 aaasgfaypg tsertgssss ssssavvaar peappakecp aptpaaaaaa ppsapalgyg 121 yhfgngyysc rmshgvglqq nalkssphas lggfpvekym dvsglasssv panevparak 181 evsfyqgyts pyqhvpgyid mvstfgsgep rheayismeg yqswtlangw nsqvyctkdq 241 pqgshfwkss fpgdvalnqp dmcvyrrgrk krvpytklql keleneyain kfinkdkrrr 301 isaatnlser qvtiwfqnrr vkdkkivskl kdtvs

An exemplary human HOXD13 nucleic acid sequence is set forth below (SEQ ID NO: 50; GenBank Accession No: NM_000523.3, Version 3, incorporated herein by reference):

   1 gagaaaggag aggagggagg aggcgcgccg cgccatggtg tcctgcgcgg ggccagggcc   61 agggccgggg ccgggccagg ccgggccatg agccgcgccg ggagctggga catggacggg  121 ctgcgggcag acggcggggg cgccggtggc gccccggcct cttcctcctc ctcatcggtg  181 gcggcggcgg cggcgtcagg ccagtgccgc ggctttctct ccgcgcctgt gttcgccggg  241 acgcattcgg ggcgggcggc ggcggcggca gcggcggctg cggcggcggc ggcggcagcc  301 tccggctttg cgtaccccgg gacctctgag cgcacgggct cttcctcgtc gtcgtcctct  361 tctgccgttg tagcggcgcg cccggaggct cccccagcca aagagtgccc agcacccacg  421 cctgcagcgg ccgctgcagc gcccccgagc gctccagcgc tgggctacgg ctaccacttc  481 ggcaacggct actacagctg ccgtatgtcg cacggcgtgg gcttacagca gaatgcgctc  541 aagtcatcgc cgcacgcctc gctgggaggc tttcccgtgg agaagtacat ggacgtgtca  601 ggcctggcga gcagcagcgt accggccaac gaggtgccag cgcgagccaa ggaggtatcc  661 ttctaccagg gctatacgag cccttaccag cacgtgcccg gctatatcga catggtgtcc  721 actttcggct ccggggagcc tcggcacgag gcctacatct ccatggaggg gtaccagtcc  781 tggacgctgg ctaacgggtg gaacagccag gtgtactgca ccaaggacca gccacagggg  841 tcccactttt ggaaatcttc ctttccaggg gatgtggctc taaatcagcc ggacatgtgc  901 gtctaccgaa gagggaggaa gaagagagtg ccttacacca aactgcagct taaagaactg  961 gagaacgagt atgccattaa caaattcatt aacaaggaca agcggcggcg tatctcggct 1021 gctacgaacc tatctgagag acaagtgacc atttggtttc agaaccgaag agtgaaggac 1081 aagaaaattg tctccaagct caaagatact gtctcctgat gtggtccagg ttggccacag 1141 acagcttaga agccattcgg ttgtctccaa aaggcctttg gaaagacttg aatatgtatt 1201 taattccccc caccccctgc caatggtggc aaattttgtg aattgttttt ctctcttccc 1261 cttatctggc tctaaaacct tctgctgccc aacctgactt tgtagttctg atttttactt 1321 gtttattatt ggttttgttc ttgcctaggg tttttaaaat atctgttttt aatgttttgt 1381 ttctccctcc aggccagtat aaagggactt gaagtatttt ttaataatcc gccccccaat 1441 gaacttcaga agtgccattc tgatttaagg gtttttttaa aaaattactt tatttgttca 1501 ttcccagcac tgattatctt cataatccat taggacagaa tggttttcag tcgttcatat 1561 cctgtaatta ggtaattgaa tcattagctc tcagcagttg ccctgaggca agtggaaagg 1621 caggcagtgc tctggggtca ccgagaaagt ctaaaaacag gaggctgaag gtactgtgat 1681 ggctttaaaa atggccacct tattaaatag ggattgtatc aatattgaaa tgaagacaat 1741 ctttccaact ttgggtgttt cacttgctgt tttaattgtt tgtttttaac actttgtagg 1801 tttgtgtttt cataatcttt aatttgaaac tcatgtgtcc tcatggatcg tggatgcctt 1861 catttcttga gctctcaatg cagacattta aatggctgca atcagtagag tgacccgcgg 1921 atggcataaa tgcacctcct tttcttggcc ttggatctat gggtctggga ttgtggtcat 1981 ctcctcaatc ctcaaaaaga ggctgaatca atgtggccgt gggtgggaac ttacatacag 2041 aacccaatga agaacttgac tgtctaaaca agggggcctc gcatggagct gtaaagcatc 2101 taacaaatat gaaaaatgtg aagttccaag gtccaagaag aaaaataatg atgtttctga 2161 aagtgatgat aaataattac ttttaaagtg ctgcatattt atacaattga gagattattt 2221 ttgtaaatgc aatgtctgtg agctgggata catgggcagt gcttcagaca tttaaaaatc 2281 actttttact cctagggaga tgccaataaa cagaactctt ttgtttcaaa aaaaaaaaaa 2341 a

An exemplary human HOXD11 amino acid sequence is set forth below (SEQ ID NO: 51; GenBank Accession No: AAI09395.1, Version 1, incorporated herein by reference):

  1 mylpgcayyv apsdfaskps flsqpsscqm tfpyssnler gggspctkat pgsepkgaae  61 gsggdgegpp geagaeksss avapqrsrkk rcpytkyqir elerefffnv yinkekrlql 121 srmlnltdrq vkiwfqnrrm kekklnrdrl qyftgnplf

An exemplary human HOXD11 nucleic acid sequence is set forth below (SEQ ID NO: 52; GenBank Accession No: NM_021192.2, Version 2, incorporated herein by reference):

   1 atgaacgact ttgacgagtg cggccagagc gcagccagca tgtacctgcc gggctgcgcc   61 tactatgtgg ccccgtctga cttcgctagc aagccttcgt tcctttccca accgtcgtcc  121 tgccagatga ctttccccta ctcttccaac ctggctccgc acgtccagcc cgtgcgcgaa  181 gtggccttcc gcgactacgg cctggagcgc gccaagtggc cgtaccgcgg cggcggcggc  241 ggcggcagcg cggggggcgg cagcagcggg ggcggccccg gcgggggcgg cggcggcgcg  301 gggggctacg ctccctacta cgcggcggcg gcggcggcgg ctgcggcggc cgcggcggcc  361 gaggaggcgg ccatgcaacg cgagcttctc ccgcccgcgg gccgccggcc ggacgtgctc  421 ttcaaggcgc ctgagccggt gtgcgctgcg ccggggccgc cgcacggccc cgcgggcgcc  481 gcctccaact tctacagcgc ggtgggccgc aatggcatct tgccacaggg cttcgaccag  541 ttctacgagg cagcgcccgg gcccccgttc gccgggccgc agcccccgcc gccacccgcg  601 ccgccacagc ccgagggcgc agccgacaag ggcgacccca ggaccggggc tggtggcggc  661 gggggcagtc cctgcaccaa ggcgacccct ggctcggagc ccaagggggc agcagaaggc  721 agcggtggcg acggcgaggg ccccccggga gaggcggggg ccgagaagag cagcagcgca  781 gttgcccccc agcggtcccg gaaaaagcgc tgtccctata ccaagtacca gatccgcgaa  841 ctggaacgcg agtttttctt taacgtgtac ataaacaaag agaaaagact tcaactctct  901 cggatgctca acctcactga ccggcaagtc aaaatctggt tccagaatcg caggatgaaa  961 gaaaagaaac tgaacagaga ccgtctgcag tatttcactg gaaacccctt attttgagag 1021 ctccaggaag cgccctcacc ccagccccac tcacccaccc tccttcccac cagcctgctc 1081 tccgcaggcc cactgtcctt gggtttaatg acgtctcttc tctgtggaac ttcacgattc 1141 cttcccacgg tcaactcggg acctcccagc gaccactgca gcctgcggac gaggccggga 1201 cttggccgag cggatcctaa taaggggaaa atggtaaatg caaacgtccc gttacaattt 1261 taccgccagt gtgctgtcgt tccccctccc cctctccgag tcctcgtggg gacacggcgg 1321 ggtctgtagg aagttgggcc gggttggggg ttgctagaag gcgctggtgt tttgctctga 1381 gttttaagag atcccttcct tcctcttcgg tgaatgcagg ttatttaaac tttgggaaat 1441 gtacttttag tctgtcatat caa

An exemplary human HOXA2 nucleic acid sequence is set forth below (SEQ ID NO: 53; GenBank Accession No: NM_006726.1, Version 1, incorporated herein by reference):

  1 mnyefereig finsqpslae cltsfppvad tfqsssikts tlshstlipp pfeqtipsln  61 pgshprhgag grpkpspags rgspvpagal qppeypwmke kkaakktall paaaaaataa 121 atgpaclshk esleiadgsg ggsrrlrtay tntqllelek efhfnkylcr prrveiaall 181 dlterqvkvw fqnrrmkhkr qtqckenqns egkcksleds ekveedeeek tlfeqalsvs 241 galleregyt fqgnalsqqq apnghngdsq sfpvspltsn eknlkhfqhq sptvpnclst 301 mgqncgagln ndspealevp slqdfsvfst dsclqlsdav spslpgslds pvdisadsld 361 fftdtlttid lqhlny

An exemplary human HOXA2 nucleic acid sequence is set forth below (SEQ ID NO: 54; GenBank Accession No: NM_006735.3, Version 3, incorporated herein by reference):

   1 tcttttgatt aaagcccaaa ttgtcattgg gcagaagcaa tcatgtgaca gccaattcgg   61 tccaatttca accttgtctc catgaattca atagtttaat agtagcgcgg tccccatacg  121 gctgtaatca gtgaattaga aaaaaaacac cctagcagcg atattctatg atagattttt  181 tttcctctgc gctcgccttt ttcctaggcc ttgccccccc aaagcccctc caaaagaggg  241 aactttttct ctgagggggc tccaaggaga aggccatgaa ttacgaattt gagcgagaga  301 ttggttttat caatagccag ccgtcgctcg ctgagtgcct gacatctttt ccccctgtcg  361 ctgatacatt tcaaagttca tcaatcaaga cctcgacgct ttcacactcg acactgattc  421 ctcctccttt tgagcagacc attcccagcc tgaaccccgg cagtcaccct cgccacggcg  481 ctggcggccg ccccaagccg agccccgcgg gcagccgcgg cagcccggtg cccgccggcg  541 ccctgcagcc gcccgagtac ccctggatga aggagaagaa ggcggccaag aaaaccgcac  601 ttctgccggc cgccgccgcc gccgccaccg ccgcagccac cggccctgct tgcctcagcc  661 acaaagaatc cctggaaatc gccgatggca gcggcggggg atcgcggcgc ctgagaactg  721 cttacaccaa cacacagctt ctagagctgg aaaaagaatt tcatttcaac aagtaccttt  781 gcagaccccg aagggtggag attgcagcgc tgctggattt gactgagaga caagtgaaag  841 tgtggtttca gaaccggagg atgaagcaca agaggcagac ccagtgcaag gaaaaccaaa  901 acagcgaagg gaaatgtaaa agccttgagg actccgagaa agtagaggag gacgaggaag  961 agaagacgct ctttgagcaa gcccttagcg tctctggggc ccttctggag agggaaggct 1021 acacttttca gcaaaatgcc ctctctcagc agcaggctcc caatggacac aatggcgact 1081 cccaaagttt cccagtctcg cctttaacca gcaatgagaa aaatctgaaa cattttcagc 1141 accagtcacc cactgttccc aactgcttgt caacaatggg ccagaactgt ggagctggcc 1201 taaacaatga cagtcctgag gcccttgagg tcccctcttt gcaggacttt agcgttttct 1261 ccacagattc ctgcctgcag ctttcagatg cagtttcacc cagtttgcca ggttccctcg 1321 acagtcccgt agatatttca gctgacagct tagacttttt tacagacaca ctcaccacaa 1381 tcgacttgca gcatctgaat tactaaaaac attaaagcaa aacaaagcat caccaaacaa 1441 aaactccttt gaccaggtgg ttttgccttc ttttatttgg gagtttattt tttattttct 1501 tcttgaccta ccccttccct cctttaagtg ttgaggattt tctgtttagt gattccctga 1561 cccagtttca aacagagcca tcttttacag attattttgg agttttagtt gttttaaacc 1621 taactcaaca accctttatg tgattcctga gagcagtatg aggcctgcaa gaaagtgatc 1681 atataattgt atcttcactt tctttttatt tttgtattac attgggatgc attgtcatgc 1741 atattttttg tagaataaat tctcctttgc tataagtaaa aaaaaaaaaa a

An exemplary human HOXA5 amino acid sequence is set forth below (SEQ ID NO: 55; GenBank Accession No: P20719.2, Version 2, incorporated herein by reference):

  1 mssyfvnsfc grypngpdyq lhnygdhssv seqfrdsasm hsgrygygyn gmdlsvgrsg  61 sghfgsgera rsyaasasaa paeprysqpa tsthspqpdp lpcsavapsp gsdshhggkn 121 slsnssgasa dagsthissr egvgtasgae edapasseqa saqsepspap paqpqiypwm 181 rklhishdni ggpegkrart aytryqtlel ekefhfnryl trrrrieiah alclserqik 241 iwfqnrrmkw kkdnklksms maaaggafrp

An exemplary human HOXA5 nucleic acid sequence is set forth below (SEQ ID NO: 56; GenBank Accession No: NM_019102.3, Version 3, incorporated herein by reference):

   1 gggtgctata gacgcacaaa cgaccgcgag ccacaaatca agcacacata tcaaaaaaca   61 aatgagctct tattttgtaa actcattttg cggtcgctat ccaaatggcc cggactacca  121 gttgcataat tatggagatc atagttccgt gagcgagcaa ttcagggact cggcgagcat  181 gcactccggc aggtacggct acggctacaa tggcatggat ctcagcgtcg gccgctcggg  241 ctccggccac tttggctccg gagagcgcgc ccgcagctac gctgccagcg ccagcgcggc  301 gcccgccgag cccaggtaca gccagccggc cacgtccacg cactctcctc agcccgatcc  361 gctgccctgc tccgccgtgg ccccctcgcc cggcagcgac agccaccacg gcgggaaaaa  421 ctccctaagc aactccagcg gcgcctcggc cgacgccggc agcacccaca tcagcagcag  481 agagggggtt ggcacggcgt ccggagccga ggaggacgcc cctgccagca gcgagcaggc  541 gagtgcgcag agcgagccga gcccggcgcc gcccgcccaa ccccagatct acccctggat  601 gcgcaagctg cacataagtc atgacaacat aggcggcccg gaaggcaaaa gggcccggac  661 ggcctacacg cgctaccaga ccctggagct ggagaaggag ttccacttca accgttacct  721 gacccgcaga aggaggattg aaatagcaca tgctctttgc ctctccgaga gacaaattaa  781 aatctggttc caaaaccgga gaatgaagtg gaaaaaagat aataagctga aaagcatgag  841 catggccgcg gcaggagggg ccttccgtcc ctgagtatct gagcgtttaa agtactgagc  901 agtattagcg gatcccgcgt agtgtcagta ctaaggtgac tttctgaaac tcccttgtgt  961 tccttctgtg aagaagccct gttctcgttg ccctaattca tcttttaatc atgagcctgt 1021 ttattgccat tatagcgcct gtataagtag atctgctttc tgttcatctc tttgtcctga 1081 atggctttgt cttgaaaaaa aatagatgtt ttaacttatt tatatgaagc aagctgtgtt 1141 acttgaagta actataacaa aaaaagaaaa gagaaaaaaa aacacacaaa aagtccccct 1201 tcaatctcgt ttagtgccaa tgttgtgtgt tgcactcaag ttgtttaact gtgcatgtgc 1261 gtggaagtgt tcctgtctca atagctccaa gctgttaaag atatttttat tcaaactacc 1321 tatattcctt gtgtaattaa tgctgttgta gaggtgactt gatgagacac aacttgttcg 1381 acgtgtagtg actagtgact ctgtgatgaa aactgtgact ccaagcggtg tgtccctgcg 1441 tgcctttata ggaccctttg cacgaactct ggaagtggct cttataagcg cagcttcagt 1501 gatgtatgtt tttgtgaaca aagttacaaa tattgtccaa gtctggctgt tttaagcaaa 1561 ctgtgatcag cttttttttt tttttttttt tttttgtatt tgtttttaag gaaaaaatac 1621 tgactggaac aaaaaataaa ctttctattg taagttc

An exemplary human HOXD10 amino acid sequence is set forth below (SEQ ID NO: 57; GenBank Accession No: P28358.2, Version 2, incorporated herein by reference):

  1 msfpnsspaa ntflvdslis acrsdsfyss sasmymppps admgtygmqt cgllpslakr  61 evnhqnmgmn vhpyipqvds wtdpnrscri eqpvtqqvpt csfttnikee snccmysdkr 121 nklisaevps yqrlvpescp venpevpvpg yfrlsqtyat gktqeynnsp egsstvmlql 181 nprgaakpql saaqlqmekk mnepvsgqep tkvsqvespe akgglpeers claevsvssp 241 evqekeskee iksdtptsnw ltaksgrkkr cpytkhqtle lekeflfnmy ltrerrleis 301 ksvnltdrqv kiwfqnrrmk lkkmsrenri reltanltfs

An exemplary human HOXD10 nucleic acid sequence is set forth below (SEQ ID NO: 58; GenBank Accession No: NM_002148.3, Version 3, incorporated herein by reference):

   1 cggggaatgt tttcctagag atgtcagcct acaaaggaca caatctctct tcttcaaatt   61 cttccccaaa atgtcctttc ccaacagctc tcctgctgct aatacttttt tagtagattc  121 cttgatcagt gcctgcagga gtgacagttt ttattccagc agcgccagca tgtacatgcc  181 accacctagc gcagacatgg ggacctatgg aatgcaaacc tgtggactgc tcccgtctct  241 ggccaaaaga gaagtgaacc accaaaatat gggtatgaat gtgcatcctt atatacctca  301 agtagacagt tggacagatc cgaacagatc ttgtcgaata gagcaacctg ttacacagca  361 agtccccact tgctccttca ccaccaacat taaggaagaa tccaattgct gcatgtattc  421 tgataagcgc aacaaactca tttcggccga ggtcccttcg taccagaggc tggtccctga  481 gtcttgtccc gttgagaacc ctgaggttcc cgtccctgga tattttagac tgagtcagac  541 ctacgccacc gggaaaaccc aagagtacaa taatagcccc gaaggcagct ccactgtcat  601 gctccagctc aaccctcgtg gcgcggccaa gccgcagctc tccgctgccc agctgcagat  661 ggaaaagaag atgaacgagc ccgtgagcgg ccaggagccc accaaagtct cccaggtgga  721 gagccccgag gccaaaggcg gccttcccga agagaggagc tgcctggctg aggtctccgt  781 gtccagtccc gaagtgcagg agaaggaaag caaagaggaa atcaagtctg atacaccaac  841 cagcaattgg ctcactgcaa agagtggcag aaagaagagg tgcccttaca ctaagcacca  901 aacgctggaa ttagaaaaag agttcttgtt caatatgtac ctcacccgcg agcgccgcct  961 agagatcagt aagagcgtta acctcaccga caggcaggtc aagatttggt ttcaaaaccg 1021 ccgaatgaaa ctcaagaaga tgagccgaga gaaccggatc cgagaactga ccgccaacct 1081 cacgttttct taggtctgag gccggtctga ggccggtcag aggccaggat tggagagggg 1141 gcaccgcgtt ccagggccca gtgctggagg actgggaaag cggaaacaaa accttcaccg 1201 ctctttgttt gttgttttgt tgtattttgt tttcctgcta gaatgtgact ttggggtcat 1261 tatgttcgtg ctgcaagtga tctgtaatcc ctatgagtat atatatatat atatatatat 1321 atatataaaa acttagcacg tgtaatttat tattttttca tcgtaatgca gggtaactat 1381 tattgcgcat tttcatttgg gtcttaactt attggaactg tagagcatcc atccatccat 1441 ccatccagca atgtgacttt ttcatgtctt tcctaacaca aaaggtctat gtgtgtggtt 1501 agtccatgaa ctcatggcat tttgaataca tccagtactt taaaaatgac atatatattt 1561 aaaaaaaaaa gattaagaaa acccacaagt tggagggagg gggacttaaa aagcacatta 1621 caatgtatct tttcacaaat gaatttagca gttgtccttg gtgagatggg atattggcga 1681 tttatgcctt gtagcctttc ccttgtggtg catctgtggt ttggtagaag tacaacagca 1741 acctgtcctt tctgtgcatg ttctggtcgc atgtataatg caataaactc tggaaatgag 1801 ttcaaaaaaa aaaa

An exemplary human ANGPT1 amino acid sequence is set forth below (SEQ ID NO: 59; GenBank Accession No: AAI52420.1, Version 1, incorporated herein by reference):

  1 mtvflsfafl aailthigcs nqrrspensg rrynriqhgq caytfilpeh dgncresttd  61 qyntnalqrd aphvepdfss qklqhlehvm enytqwlqkl enyivenmks emaqiqqnav 121 qnhtatmlei gtsllsqtae qtrkltdvet qvlnqtsrle iqllenslst yklekqllqq 181 tneilkihek nsllehkile megkhkeeld tlkeekenlq glvtrqtyii qelekqlnra 241 ttnnsvlqkq qlelmdtvhn lvnlctkegv llkggkreee kpfrdcadvy qagfnksgiy 301 tiyinnmpep kkvfcnmdvn gggwtviqhr edgsldfqrg wkeykmgfgn psgeywlgne 361 fifaitsqrq ymlrielmdw egnraysqyd rfhignekqn yrlylkghtg tagkqsslil 421 hgadfstkda dndncmckca lmltggwwfd acgpsnlngm fytagqnhgk lngikwhyfk 481 gpsyslrstt mmirpldf

An exemplary human ANGPT1 nucleic acid sequence is set forth below (SEQ ID NO: 60; GenBank Accession No: NM_001146.4, Version 4, incorporated herein by reference):

   1 gccctaagcc atcagcaatc cttagtatag gggcacactc atgcattcct gtcaagtcat   61 cttgtgaaag gctgcctgct tccagcttgg cttggatgtg caaccttaat aaaactcact  121 gaggtctggg agaaaatagc agatctgcag cagatagggt agaggaaagg gtctagaata  181 tgtacacgca gctgactcag gcaggctcca tgctgaacgg tcacacagag aggaaacaat  241 aaatctcagc tactatgcaa taaatatctc aagttttaac gaagaaaaac atcattgcag  301 tgaaataaaa aattttaaaa ttttagaaca aagctaacaa atggctagtt ttctatgatt  361 cttcttcaaa cgctttcttt gagggggaaa gagtcaaaca aacaagcagt tttacctgaa  421 ataaagaact agttttagag gtcagaagaa aggagcaagt tttgcgagag gcacggaagg  481 agtgtgctgg cagtacaatg acagttttcc tttcctttgc tttcctcgct gccattctga  541 ctcacatagg gtgcagcaat cagcgccgaa gtccagaaaa cagtgggaga agatataacc  601 ggattcaaca tgggcaatgt gcctacactt tcattcttcc agaacacgat ggcaactgtc  661 gtgagagtac gacagaccag tacaacacaa acgctctgca gagagatgct ccacacgtgg  721 aaccggattt ctcttcccag aaacttcaac atctggaaca tgtgatggaa aattatactc  781 agtggctgca aaaacttgag aattacattg tggaaaacat gaagtcggag atggcccaga  841 tacagcagaa tgcagttcag aaccacacgg ctaccatgct ggagatagga accagcctcc  901 tctctcagac tgcagagcag accagaaagc tgacagatgt tgagacccag gtactaaatc  961 aaacttctcg acttgagata cagctgctgg agaattcatt atccacctac aagctagaga 1021 agcaacttct tcaacagaca aatgaaatct tgaagatcca tgaaaaaaac agtttattag 1081 aacataaaat cttagaaatg gaaggaaaac acaaggaaga gttggacacc ttaaaggaag 1141 agaaagagaa ccttcaaggc ttggttactc gtcaaacata tataatccag gagctggaaa 1201 agcaattaaa cagagctacc accaacaaca gtgtccttca gaagcagcaa ctggagctga 1261 tggacacagt ccacaacctt gtcaatcttt gcactaaaga aggtgtttta ctaaagggag 1321 gaaaaagaga ggaagagaaa ccatttagag actgtgcaga tgtatatcaa gctggtttta 1381 ataaaagtgg aatctacact atttatatta ataatatgcc agaacccaaa aaggtgtttt 1441 gcaatatgga tgtcaatggg ggaggttgga ctgtaataca acatcgtgaa gatggaagtc 1501 tagatttcca aagaggctgg aaggaatata aaatgggttt tggaaatccc tccggtgaat 1561 attggctggg gaatgagttt atttttgcca ttaccagtca gaggcagtac atgctaagaa 1621 ttgagttaat ggactgggaa gggaaccgag cctattcaca gtatgacaga ttccacatag 1681 gaaatgaaaa gcaaaactat aggttgtatt taaaaggtca cactgggaca gcaggaaaac 1741 agagcagcct gatcttacac ggtgctgatt tcagcactaa agatgctgat aatgacaact 1801 gtatgtgcaa atgtgccctc atgttaacag gaggatggtg gtttgatgct tgtggcccct 1861 ccaatctaaa tggaatgttc tatactgcgg gacaaaacca tggaaaactg aatgggataa 1921 agtggcacta cttcaaaggg cccagttact ccttacgttc cacaactatg atgattcgac 1981 ctttagattt ttgaaagcgc aatgtcagaa gcgattatga aagcaacaaa gaaatccgga 2041 gaagctgcca ggtgagaaac tgtttgaaaa cttcagaagc aaacaatatt gtctcccttc 2101 cagcaataag tggtagttat gtgaagtcac caaggttctt gaccgtgaat ctggagccgt 2161 ttgagttcac aagagtctct acttggggtg acagtgctca cgtggctcga ctatagaaaa 2221 ctccactgac tgtcgggctt taaaaaggga agaaactgct gagcttgctg tgcttcaaac 2281 tactactgga ccttattttg gaactatggt agccagatga taaatatggt taatttcatg 2341 taaaacagaa aaaaagagtg aaaaagagaa tatacatgaa gaatagaaac aagcctgcca 2401 taatcctttg gaaaagatgt attataccag tgaaaaggtg ttatatctat gcaaacctac 2461 taacaaatta tactgttgca caattttgat aaaaatttag aacagcattg tcctctgagt 2521 tggttaaatg ttaatggatt tcagaagcct aattccagta tcatacttac tagttgattt 2581 ctgcttaccc atcttcaaat gaaaattcca tttttgtaag ccataatgaa ctgtagtaca 2641 tggacaataa gtgtgtggta gaaacaaact ccattactct gatttttgat acagttttca 2701 gaaaaagaaa tgaacataat caagtaagga tgtatgtggt gaaaacttac cacccccata 2761 ctatggtttt catttactct aaaaactgat tgaatgatat ataaatatat ttatagcctg 2821 agtaaagtta aaagaatgta aaatatatca tcaagttctt aaaataatat acatgcattt 2881 aatatttcct ttgatattat acaggaaagc aatattttgg agtatgttaa gttgaagtaa 2941 aagcaagtac tctggagcag ttcattttac agtatctact tgcatgtgta tacatacatg 3001 taacttcatt attttaaaaa tatttttaga actccaatac tcaccctgtt atgtcttgct 3061 aatttaaatt ttgctaatta actgaaacat gcttaccaga ttcacactgt tccagtgtct 3121 ataaaagaaa cactttgaag tctataaaaa ataaaataat tataaatatc attgtacata 3181 gcatgtttat atctgcaaaa aacctaatag ctaattaatc tggaatatgc aacattgtcc 3241 ttaattgatg caaataacac aaatgctcaa agaaatctac tatatccctt aatgaaatac 3301 atcattcttc atatatttct ccttcagtcc attcccttag gcaattttta atttttaaaa 3361 attattatca ggggagaaaa attggcaaaa ctattatatg taagggaaat atatacaaaa 3421 agaaaattaa tcatagtcac ctgactaaga aattctgact gctagttgcc ataaataact 3481 caatggaaat attcctatgg gataatgtat tttaagtgaa tttttggggt gcttgaagtt 3541 actgcattat tttatcaaga agtcttctct gcctgtaagt gtccaaggtt atgacagtaa 3601 acagttttta ttaaaacatg agtcactatg ggatgagaaa attgaaataa agctactggg 3661 cctcctctca taaaagagac agttgttggc aaggtagcaa taccagtttc aaacttggtg 3721 acttgatcca ctatgcctta atggtttcct ccatttgaga aaataaagct attcacattg 3781 ttaagaaaaa tactttttaa agtttaccat caagtctttt ttatatttat gtgtctgtat 3841 tctacccctt tttgccttac aagtgatatt tgcaggtatt ataccatttt tctattcttg 3901 gtggcttctt catagcaggt aagcctctcc ttctaaaaac ttctcaactg ttttcattta 3961 agggaaagaa aatgagtatt ttgtcctttt gtgttcctac agacactttc ttaaaccagt 4021 ttttggataa agaatactat ttccaaactc atattacaaa aacaaaataa aataataaaa 4081 aaagaaagca tgatatttac tgttttgttg tctgggtttg agaaatgaaa tattgtttcc 4141 aattatttat aataaatcag tataaaatgt tttatgattg ttatgtgtat tatgtaatac 4201 gtacatgttt atggcaattt aacatgtgta ttcttttaat tgtttcagaa taggataatt 4261 aggtattcga attttgtctt taaaattcat gtggtttcta tgcaaagttc ttcatatcat 4321 cacaacatta tttgatttaa ataaaattga aagtaatatt tgtgcaa

An exemplary human ANG2 amino acid sequence is set forth below (SEQ ID NO: 61; GenBank Accession No: AAF21627.2, Version 2, incorporated herein by reference):

  1 maaaaaagps pgsgpgdspe gpegeaperr rkahgmlkly yglsegeaag rpagpdpldp  61 tdlngahfdp evyldklrre cplaqlmdse tdmvrqiral dsdmqtivye nynkfisatd 121 tirkmkndfr kmedemdrla tnmavitdfs arisatlqdr heritklagv hallrklqfl 181 felpsrltkc velgaygqav ryggragavl qqyqhlpsfr aiqddcqvit arlaqqlrqr 241 freggsgape qaecvellla lgepaeelce eflahargrl ekelrnleae lgpsppapdv 301 leftdhggsg fvgglcqvaa ayqelfaaqg pagaeklaaf arqlgsryfa lverrlageg 361 gggdnsllvr aldrfhrrlr apgallaaag ladaateive rvarerlghh lqglraaflg 421 cltdvrqala aprvagkegp glaellanva ssilshikas laavhlftak evsfsnkpyf 481 rgefcsqgvr eglivgfvhs mcqtaqsfcd spgekggatp palllllsrl cldyetatis 541 yiltltdeqf lvqdqfpvtp vstlcaeare tarrllthyv kvqglvisqm lrksvetrdw 601 lstleprnvr avmkrvvedt taidvqvgll yeegvrkaqs sdsskrtfsv ysssrqqgry 661 apsytpsapm dtnllsniqk lfseridvfs pvefnkvsvl tgiikislkt llecvrlrtf 721 grfglqqvqv dchflqlylw rfvadeelvh llldevvasa alrcpdpvpm epsvvevice 781 rg

An exemplary human ANG2 nucleic acid sequence is set forth below (SEQ ID NO: 62; GenBank Accession No: AF024631.2, Version 2, incorporated herein by reference):

   1 ttcctttcca gcctcacgcc cgtgggctgc agttggaacg atggcggcgg cagctgccgc   61 cgggcctagc ccggggtctg gacctgggga ctccccagaa gggcccgagg gggaggctcc  121 ggagcgtcgg cggaaggcgc acgggatgct gaagctttac tacggcctct cggaagggga  181 ggcggcggga cgccccgcgg ggcccgaccc cctggacccg actgatctga acggggcgca  241 cttcgacccg gaagtttacc tagacaagct gcgtagagag tgccctctgg cccagttgat  301 ggacagtgag acggacatgg tgcggcagat ccgggctcta gacagcgaca tgcagaccct  361 ggtctatgag aactacaaca agttcatctc agccacagac accatccgga agatgaagaa  421 cgatttccgg aagatggagg atgagatgga ccggctggcc accaacatgg cagtgatcac  481 cgacttcagc gctcgcatca gcgccacgct gcaggaccgc cacgagcgca tcaccaagct  541 ggcaggggtc cacgcgctgc tgcggaagct gcagttcctc tttgagctgc cctcgcgcct  601 caccaagtgc gtggaactgg gcgcctatgg gcaggcggtg cgctaccagg gccgcgcgca  661 ggccgtgctg cagcagtacc aacacctgcc ctcgttccgc gccatccagg acgactgcca  721 ggtcatcacg gcccgcctgg cccagcagct gcggcagcgc tttagggagg gcggctcagg  781 cgccccggag caggcagagt gcgtggagct gctgctggcc ctgggcgagc ctgcggagga  841 gctgtgcgag gagttcctgg cgcacgcccg cggccggctg gagaaggagc tgagaaacct  901 ggaggccgag ctggggccct cacctccggc tcccgacgtg ttagagttca ccgaccatgg  961 aggcagtggc ttcgtgggcg gcctctgcca ggtggcggcg gcctaccagg agctgtttgc 1021 ggcccagggc ccagcaggtg ccgagaagct ggcggccttc gcccggcagc tgggcagccg 1081 ctattttgcg ctggtggagc ggcggctggc gcaggagcag ggtggtggtg acaactcact 1141 gctggtgcgg gcgctggacc gcttccaccg gcgcttgcgg gctcccgggg ccctgctggc 1201 cgctgccggg ctcgcagacg ctgccacgga gatcgtggaa cgagtggccc gcgagcgcct 1261 gggccaccac ctgcagggtc tccgggcggc cttcctgggc tgcctgacag acgtccgcca 1321 ggcgctggca gcacctcgcg tggctgggaa ggagggccct ggcctggccg agttgctggc 1381 caatgtggcc agctccatcc tgagccacat taaggcctct ctggcagcag tgcacctttt 1441 caccgccaaa gaggtgtcct tctccaacaa gccctacttc cggggtgagt tctgcagtca 1501 gggtgtccgt gagggcctca tcgtgggctt cgtccactct atgtgccaga cggctcagag 1561 cttctgcgac agccctgggg agaagggggg tgccacacca cctgccctgc tcctgctgct 1621 ctcccgcctc tgcctggact acgagacggc caccatctcc tacatcctca ctctcactga 1681 tgaacagttt ctggtgcagg atcagttccc agtgacgccc gtgagcacgc tgtgtgcaga 1741 ggccagggaa acggcgcggc ggctgctgac ccactacgtg aaggtgcagg gcctggtcat 1801 atcacagatg ctgcgcaaga gcgtggagac tcgcgactgg ctcagcactc tggagccccg 1861 gaatgtgcgg gccgtcatga agcgggtggt ggaggatacc accgccatcg acgtgcaggt 1921 ggggctcctg tacgaagagg gtgttcgcaa ggcccagagc agcgactcca gcaagaggac 1981 tttctccgtg tacagcagct ctcggcagca gggccgctac gcccccagct atacccccag 2041 tgccccgatg gacaccaacc tcttgagcaa tatccagaag ctattctctg aacgtattga 2101 tgtgttcagc cctgtggagt tcaacaaggt gtcggtgctg accggcatca tcaagatcag 2161 cctgaagacg ctgctggagt gtgtgcggct gcgcaccttt gggcgcttcg ggctgcagca 2221 ggtgcaagtg gactgccact ttctgcagct ctacctgtgg cgttttgtgg ccgacgaaga 2281 actcgtgcac ttgctgctgg acgaagtggt ggcctctgct gccctgcgct gcccagaccc 2341 tgtgcccatg gagcccagtg tggttgaggt catctgcgag cgcggctagg cgcagccgct 2401 gccatgcacc ggtctgtccc tgcaccccat ggcacccagg atctggtctc ggtggtcctt 2461 ccccgcaggc aggtgtcagg accggcctaa taaacatgtg tggcctcctc aaaaaaaaaa 2521 aaaaaaaaaa aaaaaaaaaa aaaaaa

An exemplary human PDGFA amino acid sequence is set forth below (SEQ ID NO: 63; GenBank Accession No: P04085.1, Version 1, incorporated herein by reference):

   1 mrtlacllll gcgylahvla eeaeiprevi erlarsqihs irdlqrllei dsvgsedsld   61 tslrahgvha tkhvpekrpl pirrkrsiee avpavcktrt viyeiprsqv dptsanfliw  121 ppcvevkrct gccntssvkc qpsrvhhrsv kvakveyvrk kpklkevqvr leehlecaca  181 ttslnpdyre edtgrpresg kkrkrkrlkp t

An exemplary human PDGFA nucleic acid sequence is set forth below (SEQ ID NO: 64; GenBank Accession No: AH002927.2, Version 2, incorporated herein by reference):

   1 ttcgctccca cccggtgccg cagattgcag ctggcactgg agggtgggca agctcgaggg   61 aggggcgcgg agcgcgcgga cgcgcgcggg gctttgatgg atttagctgc ttgcgcgagc  121 gcgtgtgtgc tccctgccgc ggcggcgccc gggccctgcc gggtccgcac gaaccccgag  181 cgcttccgag gtgcgggtcc caggcccgga atccggggag gcgggggggg gggcgggggc  241 gggggcgggg gaggggcgcg gcggcggcgg ctataaccct ctccccgccg ccggccggct  301 ccacacgcgc gccctgcgga gcccgcccaa ctccggcgag ccggcctgcg cctactcctc  361 ctcctcctct cccggcggcg gctgcggcgg aggcgcgact cgccttcgcc cgccctcagg  421 cccgcgcggg cggcgcagcg aggccccggg cggcgggtgg tggctgccag cggcgtcggc  481 cggccgctgc ccggccccgg cgagcggagg gcggagcgcg gcgccggagc cgagggccgc  541 cgcggagggg gtgctgggcc gcgctgtgcc cggccgggcg gcggctgcaa gaggaggccg  601 gaggcgagcg cggggccggc ggtgggcgcg cagggcggct cgcagctcgc agccggggcc  661 gggccaggcg ttcaggcagg tgatcggtgt ggcggcggcg gcggcggcgg ccccagactc  721 cctccggagt tcttcttcgg ggctcgatgt ccgcaaatat gcagaattac cggccgggtc  781 gctcctgaag ccagcgcggg gagcgagcgc ggcggcggcc agcaccggga acgcaccgag  841 gaagaagccc agcccccgcc ctccgcccct tccgtcccca ccccctaccc ggcggcccag  901 gaggctcccc gcgctcgcgg cgcgcactcc ctgtttctcc tcctcctggc tggcgctgcc  961 tgcctctccg cactcactgc tcgccgggcg ccgtccgcca gctccgtgct ccccgcgcca 1021 ccctcctccg ggccgcgctc cctaagggat ggtactgaat ttcgccgcca caggagaccg 1081 gctggagcgc cgccccgcgg cctcgcctct cctccgagca gccagcgcct cgggacgcga 1141 tgaggacctt ggcttgcctg ctgctcctcg gctgcggata cctcgcccat gttctggccg 1201 aggttggtgc cgcccccgcg ccccgtctca cgctcggctc ctccggcgca caccccccgc 1261 cggctggggc ccacgggctc tgcagnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 1321 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 1381 nnnnntgacc gtgtggcctc tgcttgcagg aagccgagat cccccgcgag gtgatcgaga 1441 ggctggcccg cagtcagatc cacagcatcc gggacctcca gcgactcctg gagatagact 1501 ccgtaggtaa atcgcgcccc ttccctcgcg cgcgggnnnn nnnnnnnnnn nnnnnnnnnn 1561 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 1621 nnnnnnnnnn nnnnnnaggg cccctaatgg cgggagctgt gaggggctgt gccgccaggt 1681 gcctgttccc cagtggctcc caaagctggt ctgtgggaag tgcggctgga caggcccagg 1741 gcacagcgca cggggcattc acggtgttct ccttccgcct gcagggagtg aggattcttt 1801 ggacaccagc ctgacacgtg acggggtcca tgccactaag catgtgcccg agaagaggcc 1861 cctgcccatt cggaggaaga gaagcatcgg tgagtccagg aggccgcgat gggcagggca 1921 gggccgggtc ggggtgagtc caggaggccg cgatgggcag ggcagggccg ggtggggagg 1981 aggagctgcc cgctctccca gcgcagtggc ctcatggcaa gccacccgtt ccctcctccc 2041 taaaataggc ctggccctgg tgcctctggc tctggcctct ccgagggtgt ctcctgcccn 2101 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 2161 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnt gctcctgccc acccagcccc 2221 tgagcctctg ctcccagctc agcctctgct gcctgggagg aatcctggcc tgtgggttac 2281 cctggttgcc ccccaggccc agctggagcc gcctcagccc tggggtgggg ccgtggtcgc 2341 agaggccggt ccccgctcac tgtgcccccg ccgttgcaga ggaagctgtc cccgctgtct 2401 gcaagaccag gacggtcatt tacgagattc ctcggagtca ggtcgacccc acgtccgcca 2461 acttcctgat ctggcccccg tgcgtggagg tgaaacgctg caccggctgc tgcaacacga 2521 gcagtgtcaa gtgccagccc tcccgcgtcc accaccgcag cgtcaaggtg agcnnnnnnn 2581 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 2641 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnctgcagc ttgtaggttt tcacctggta 2701 ctgctacact ccccaccaca aggtagtgtt tctgggagga ggtcaggggt caggctgctc 2761 tctcctccct ctcagcctgt ccccggctcc cagcacgtcg tgatgtccga agctccatgc 2821 aggcattcat ggccgggctc tgttctctct ggcaggtggc caaggtggaa tacgtcagga 2881 agaagccaaa attaaaagaa gtccaggtga ggttagagga gcatttggag tgcgcctgcg 2941 cgaccacaag cctgaatccg gattatcggg aagaggacac gggtgagtgg ctgccttcgt 3001 cggcatcgtg ttggagaaca ggtcttcaga gccttgcttt tggggtgtta ggtggccccc 3061 ttgagcgcaa cgcttactgc tgtgagcatc tgggctgctg ttgaaggatt cgttgccctg 3121 ctcccgggcc agatgcctgc gggggagacg gatccnnnnn nnnnnnnnnn nnnnnnnnnn 3181 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 3241 nnnnnnnnnn nnnnntctcg gtgccagggt gctggccttc tcttctggaa agataaagaa 3301 atgccgtagg tatttgttgc ttcagttctt caccccgacg gccgtccctc ggcccactca 3361 ccgccctgcc cttttgttaa caggaaggcc tagggagtca ggtaaaaaac ggaaaagaaa 3421 aaggttaaaa cccacctaaa gcagccaacc aggtaggact gtctgccgga cactgagtcc 3481 tgctaggcat gcaagnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn 3541 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnctgca 3601 gatgtgaggt gaggatgagc cgcagccctt tcctgggaca tggatgtaca tggcgtgtta 3661 cattcctgaa cctactatgt acggtgcttt attgccagtg gcggtctttg ttctcctccg 3721 tgaaaaactg tgtccgagaa cactcgggag aacaaagaga cagtgcacat ttgtttaatg 3781 tgacatcaag caagtattgt agcactcggt gaagcagtaa gaagcttcct tgtcaaaaag 3841 agagagagag agagagagag agaaaacaaa accacaaatg acaaaaacaa aacggactca 3901 caaaaatatc taaactcgat gagatggagg gtcgccccgt gggatggaag tgcagaggtc 3961 tcagcagact ggatttctgt ccgggtggtc acagctgctt ttttgccgag gatgcagagc 4021 ctgctttggg aacgactcca gaggggtgcg tggtgggctc tgcaggggcc cgcaggaagc 4081 aggaatgtct tggaaaccgc cacggaaact ttagaaacca cacctcctcg ctgtagtatt 4141 taagcccata cagaaacctt cctgagagcc ttaagtggtt tttttttttg tttttgtttt 4201 gttttttttt tttttgtttt tttttttttt tttttacacc ataaagtgat tattaagctt 4261 tttactcttt tgctagcttt tttttttttt ttttttaatt atctctcgga tgacattcac 4321 acccacaaca cacaggctgc tgtaactgtc aggacagtgc gacggtattt ttcctagcaa 4381 gatgcaaact aatgagatgt attaaaataa acatggtata cctcctatgc atcatttcct 4441 aaatctttct ggctttgtgt ttctccctta ccctgcttta tttcttaatt taagccattt 4501 tgaagaacta tgcgtcaacc aatcgtacgc ctcctgcggc actgcccaga gccc

An exemplary human PCDHB2 amino acid sequence is set forth below (SEQ ID NO: 65; GenBank Accession No: EAW61983.1, Version 1, incorporated herein by reference):

   1 meagegkerv pkqrqvliff vllgiaqasc qprhysvaee tesgsfvanl lkdlgleige   61 lavrgarvvs kgkkmhlqfd rqtgdlllne kldreelcgp tepcvlpfqv llenplqffq  121 aelrirdvnd hspvfldkei llkipesitp gttflieraq dldvgtnslq nytispnfhf  181 hlnlqdsldg iilpqlvinr aldreeqpei rltltaldgg spprsgtalv rievvdindn  241 vpefakllye vqipedspvg sqvaivsard ldigtngeis yafsqasedi rktfrlsaks  301 gelllrqkld fesiqtytvn iqatdgggls gtcvvfvqvm dlndnppelt mstlinqipe  361 nlqdtliavf svsdpdsgdn grmvcsiqdd lpfflkpsve nfytlvista ldretrseyn  421 ititvtdfgt prlktehnit vlvsdvndna paftqtsytl fvrennspal higsvsatdr  481 dsgtnaqvty sllppqdphl plaslvsina dnghlfalqs ldyealqafe frvgaadrgs  541 palssealvr vlvldandns pfvlyplqng sapctelvpr aaepgylvtk vvavdgdsgq  601 nawlsyqllk atepglfgvw ahngevrtar llrerdaakq rlvvlvkdng epprsatatl  661 hvllvdgfsq pylllpeaap aqaqadlltv ylvvalasvs slflfsvllf vavrlcrrsr  721 aasvgrcsvp egpfpgqmvd vsgtgtlsqs yqyevcltgg sgtnefkflk piipnfvaqg  781 aervseanps frksfeft

An exemplary human PCDHB2 nucleic acid sequence is set forth below (SEQ ID NO: 66; GenBank Accession No: NM_018936.3, Version 3, incorporated herein by reference):

   1 ccttacccag atactcagct aaagaagcag caagcaggaa gaggaggctt tctaaggcgg   61 tcgctccggg aaatccgggc cctaggattg tccactcatc ccagtatcag cgagatacgg  121 ggagatagag ttagcgacaa cgtgagccag agctggagca cgtttggtga gagaccagaa  181 agcaatggag gccggagagg ggaaggagcg cgttccgaaa caaaggcaag tcctgatatt  241 ctttgttttg ctgggcatag ctcaggctag ttgccagcct aggcactatt cagtggccga  301 ggaaacggag agtggctcct ttgtggccaa tttgttaaaa gacctggggc tggagatagg  361 agaacttgct gtgagggggg ccagggtcgt ttccaaagga aaaaaaatgc atttgcagtt  421 cgataggcag accggggatt tgttgttaaa tgagaaattg gaccgggagg agctgtgcgg  481 ccccacagag ccctgtgtcc tacctttcca ggtgttacta gaaaatccct tgcagttttt  541 tcaggcggag ctacggatta gggacgtaaa tgatcattcc ccagttttcc tagacaaaga  601 aatacttttg aaaattccag aaagtatcac tcctggaact actttcttaa tagaacgtgc  661 ccaggacttg gatgtaggaa ccaacagtct ccaaaattac acaatcagtc ccaatttcca  721 ctttcatctt aatttacaag acagtctcga tggcataata ttaccacagc tggtgctgaa  781 cagagccctg gatcgcgagg agcagcctga gatcaggtta accctcacag cgctagatgg  841 cgggagtcca cccaggtccg gcacggccct ggtacggatt gaagttgtgg acatcaatga  901 caacgtccca gagtttgcaa agctgctcta tgaggtgcag atcccggagg acagccccgt  961 tggatcccag gttgccatcg tctctgccag ggatttagac attggaacta atggagaaat 1021 atcttatgca ttttcccaag catctgaaga cattcgcaaa acgtttcgat taagtgcaaa 1081 atcgggagaa ctgcttttaa gacagaaact ggatttcgaa tccatccaga catacacagt 1141 aaatattcag gcgacagatg gtgggggcct atctggaact tgtgtggtat ttgtccaagt 1201 gatggatttg aatgacaatc ctccggaact aactatgtcg acacttatca atcagatccc 1261 agaaaacttg caggacaccc tcattgctgt attcagcgtt tcagatcctg actccggaga 1321 caacggaagg atggtgtgct ccatccaaga tgatcttcct tttttcttga aaccttctgt 1381 tgagaacttt tacactctgg tgataagcac ggccctggac cgggagacca gatccgaata 1441 caacatcacc atcaccgtca ccgacttcgg gacacccagg ctgaaaaccg agcacaacat 1501 aaccgtgctg gtctccgacg tcaatgacaa cgcccccgcc ttcacccaaa cctcctacac 1561 cctgttcgtc cgcgagaaca acagccccgc cctgcacatc ggcagcgtca gcgccacaga 1621 cagagactcg ggcaccaacg cccaggtcac ctactcgctg ctgccgcccc aggacccgca 1681 cctgcccctc gcctccctgg tctccatcaa cgcggacaac ggccacctgt tcgctctcca 1741 gtcgctggac tacgaggccc tgcaggcgtt cgagttccgc gtgggcgccg cagaccgcgg 1801 ctccccggcg ttgagcagcg aggcgctggt gcgcgtgctg gtgctggacg ccaacgacaa 1861 ctcgcccttc gtgctgtacc cgctgcagaa cggctccgcg ccctgcaccg agctggtgcc 1921 ccgggcggcc gagccgggct acctggtgac caaggtggtg gcggtggacg gcgactcggg 1981 ccagaacgcc tggctgtcgt accagctgct caaggccacg gagcccgggc tgttcggcgt 2041 gtgggcgcac aatggcgagg tgcgcaccgc caggctgctg agggagcgcg acgctgccaa 2101 gcagaggctg gtggtgctgg tcaaggacaa tggcgagcct ccgcgctcgg ccaccgccac 2161 gctgcacgtg ctcctggtgg acggcttctc ccagccctac ctgctgctcc cggaggcggc 2221 accggcccag gcccaggccg acttgctcac cgtctacctg gtggtggcgt tggcctcggt 2281 gtcttcgctc ttcctcttct cggtgctcct gttcgtggcg gtgcggctgt gcaggaggag 2341 cagggcggcc tcggtgggtc gctgctcggt gcccgagggc ccctttccag ggcagatggt 2401 ggacgtgagc ggcaccggga ccctgtccca gagctaccag tacgaggtgt gtctgactgg 2461 aggctccggg acaaatgagt tcaagttcct gaagccaatt atccccaact tcgttgctca 2521 gggtgcagag agggttagcg aggcaaatcc cagtttcagg aagagctttg aattcactta 2581 agtgttaata aggatctact gaggctagtc tcgtttaatt tgtggaaagt ccttttttac 2641 tgctttgccc attggaggtg tctcctttta ttagaaagta accatcttat tccaattcta 2701 tgcatgttac tggtatttat aaatgtatga gtttttttgc ggtataataa atgtaaattt 2761 tctttgtatt ctaaaaaaa

An exemplary human PCDHB3 amino acid sequence is set forth below (SEQ ID NO: 67; GenBank Accession No: EAW61981.1, Version 1, incorporated herein by reference):

   1 meaggerflr qrqvlllfvf lggslagses rrysvaeeke kgflianlak dlglrveela   61 argaqvvskg nkqhfqlshq tgdlllnekl dreelcgpte pcilhfqill qnplqfvtne  121 lriidvndhs pvffenemhl kilestlpgt viplgnaedl dvgrnslqny titpnshfhv  181 ltrsrrdgrk ypelvldkal dreeqpelsl tltaldggsp prsgtaqini qvldindnap  241 efaqplyeva vlentpvnsv ivtvsasdld tgsfgtisya ffhaseeirk tfqlnpitgd  301 mqlvkylnfe ainsyevdie akdggglsgk stvivqvvdv ndnppeltls svnspipens  361 getvlavfsv sdldsgdngr vmcsiennlp fflkpsvenf ytlvsegald retrseynit  421 ititdlgtpr lktkynitvl vsdvndnapa ftqisytlfv rennspalhi gsvsatdrds  481 gtnaqvtysl lppqdphlpl sslvsinadn ghlfalrsld yealqafefr vgatdrgspa  541 lssealvrvl vldandnspf vlyplqngsa pctelvpraa epgylvtkvv avdgdsgqna  601 wlsyqllkat epglfgvwah ngevrtarll serdaakhrl vvlvkdngep prsatatlhv  661 llvdgfsqpy lplpeaapaq aqadlltvyl vvalasvssl flfsvllfva vrlcrrsraa  721 svgrcsvpeg pfpgqmvdvs gtgtlsqsyq yevcltggsg tnefkflkpi ipnfvaqgae  781 rvseanpsfr ksfefs

An exemplary human PCDHB3 nucleic acid sequence is set forth below (SEQ ID NO: 68; GenBank Accession No: NM_018937.4, Version 4, incorporated herein by reference):

   1 tgctcgtaga taaaagtgca ttttatttcc ctagattgca tttatttaat tcatataaca   61 tgagaaactc ctccagtagc gtcaactagg gttgataaga ataatcgata aagcaaaata  121 aaaacacctt ctccaagatt ttgtaactgc aagcgaacgc atggtggcgc tgttgactaa  181 gaaggcgaat taaaccacag gcattgtgca tgctcggtga cgcacggatc cagtgtggta  241 aaccagcggt tgagagccca ggcagatttt tgagccagca agtctgagcc tctggaaagg  301 cttattcact aggccgtcta caaaggttgt ggggcaaaag actgtttccc agctctgtct  361 gaggttcagc ttggcgacat tccctggaag agcgtgacgg aaagtgcaat ggaggcggga  421 ggagagcgat ttcttagaca aaggcaagtc ttgcttctct ttgtttttct gggagggtct  481 ctggctgggt ccgagtcaag acgctattct gtggctgagg aaaaagagaa gggcttttta  541 atagccaacc tagcaaagga tctgggacta agggtagagg aactggccgc gaggggggcc  601 caagttgtgt ccaaagggaa caaacagcat tttcagctca gtcatcagac aggtgatttg  661 ctcctgaatg agaaattgga ccgggaggag ctatgcggcc ccacagaacc atgcatacta  721 cattttcaga tattactgca aaaccctttg caattcgtta caaacgagct ccgtatcata  781 gatgtaaatg accattctcc ggtattcttt gaaaatgaaa tgcatctgaa aatcctagaa  841 agcactctgc caggaacagt aattcctttg ggaaatgctg aggacttgga tgtgggaaga  901 aacagcctcc aaaactacac tatcactccg aattcccact tccacgtact cactcgcagt  961 cgtagggacg gaaggaagta cccggaacta gtactggata aagcgctcga tcgggaggag 1021 cagccggaac tcagcttaac gctcaccgcg ctggacggcg gctctccccc tcggtctggg 1081 acagcccaga taaacatcca ggtcttagat ataaacgaca atgcaccaga atttgcacag 1141 ccgctctatg aggttgcagt tctagagaat acccccgtta actctgtcat tgtcactgtc 1201 tcggcttctg acttagatac aggaagtttt gggacaatat catatgcatt ttttcatgct 1261 tctgaagaaa ttcgcaaaac ttttcagcta aatccaatta ctggtgatat gcaactggtc 1321 aaatatttga attttgaagc gattaatagt tatgaagtcg acatcgaggc caaggatggc 1381 ggaggcctat ccggaaagtc tacagtcata gtccaggtgg ttgatgtcaa cgacaaccca 1441 ccggaactga ccttgtcttc agtaaacagc cctattcctg agaactcggg agagactgta 1501 ctggctgttt tcagtgtttc tgatctagac tctggagaca acggaagagt gatgtgttcc 1561 attgagaaca atctcccctt cttcctgaaa ccatctgtag agaattttta caccctagtg 1621 tcagaaggcg cgctggacag agagaccaga tccgagtaca acattaccat cactatcact 1681 gacctgggga cacccaggct gaaaaccaag tacaacataa ccgtgctggt ctccgacgtc 1741 aatgacaacg cccccgcctt cacccaaatc tcctacaccc tgttcgtccg cgagaacaac 1801 agccccgccc tgcacatcgg cagtgtcagc gccacagaca gagactcagg caccaacgcc 1861 caggtaacct actcgctgct gccgccccag gacccgcacc tgcccctctc ttccctggtc 1921 tccatcaacg cggacaacgg ccacctgttt gccctcaggt cgctggacta cgaggccctg 1981 caggcgttcg agttccgcgt gggcgccaca gaccgtggct ccccggcttt gagcagcgag 2041 gcgctggtgc gcgtgctggt gctggacgcc aacgacaact cgcccttcgt gctgtacccg 2101 ctgcagaacg gctccgcgcc ctgcaccgag ctggtgcccc gggcggctga gccgggctac 2161 ctggtgacca aggtggtggc ggtggacggc gactcgggcc agaacgcctg gctgtcgtac 2221 cagctgctca aggccacgga gcccgggctg ttcggcgtgt gggcgcacaa tggcgaagtg 2281 cgcaccgcca ggctgctgag cgagcgcgac gcggccaagc acaggctggt ggtgctggtc 2341 aaggacaatg gcgagcctcc gcgctcggcc accgccacgc tgcatgtgct cctggtggac 2401 ggcttctccc agccctacct gcctctcccg gaggcggcac cggcccaggc ccaggccgac 2461 ttgctcaccg tctacctggt ggtggcattg gcctcggtgt cttcgctctt cctcttttcg 2521 gtgctcctgt tcgtggcggt gcggctgtgc aggaggagca gggcggcctc ggtgggtcgc 2581 tgctcggtgc ccgagggccc ctttccaggg cagatggtgg acgtgagcgg caccgggacc 2641 ctgtcccaga gctaccagta cgaggtgtgt ctgactggag gctccgggac aaatgagttc 2701 aagttcctga agccaattat ccccaacttc gttgctcagg gtgcagagag ggttagcgag 2761 gcaaatccca gtttcaggaa gagctttgaa ttcagttaag tgttaataag gatctactga 2821 gcctcgtctt agttaatctg tggaaagtcc ttttttactg ctttgtccat tggagaggtc 2881 ttttttggtc tggttcaagg caagtagcaa gaatagagca aaatatcaaa tccagggatg 2941 gcttaggttt cattaacagt actggaaagt agttgtgtgg ctctgaatgt tttgtatttc 3001 aatcgagaat ccttagtcga tagaacattt tgtttatata ttgattctac tttttctgta 3061 gttaatcctt gcatattctc ctttcatcct ggcttgccaa cgcagtctta attccgcctt 3121 ttttttttct aatggggagc aaaaagaaat tcactgtctt ttaatagtga tttcaaatag 3181 cttattaaaa taactccatt caaattttac attataaagc aatgtagaga gagttccaaa 3241 ccaccaattt tataatttcc cttgttgaat atattcatat aatgtgttct ataatatgcc 3301 caaagcagct ttgtctatag ttaacaaagt tttaaggata gacaagaatg tgttttcttt 3361 aataaatagt aatatatcat ctttttaggg atatagtact caaatgaaag taatttagtt 3421 cattttctgt gttgacattt gcaattaata tttcaatatt ttatgtgctt atattggcca 3481 aaatatggac acaaatatag actaatatgg gtaattaccc tttggtttat ctaaagtgtg 3541 ttcatgatga ctgaggaaaa aaattaaacc tatgccattt aaaaaaaaaa aaa

An exemplary human PCDHB6 amino acid sequence is set forth below (SEQ ID NO: 69; GenBank Accession No: EAW61978.1, Version 1, incorporated herein by reference):

   1 mmqtkvqnkk rqvaffillm lwgevgsesi qysvleetes gtfvanltkd lglrvgelas   61 rgarvvfkgn rqhlqfdpqt hdlllnekld reelcgstep cvlpfqvlle nplqffqasl  121 rvrdindhap efparemllk iseitmpgki fplkmandld tgsnglqryt issnphfhvl  181 trnrsegrkf pelvldkpld reeqpqlrlt lialdggspp rsgtseiqiq vldindnvpe  241 faqelyeaqv pennplgslv itvsardlda gsfgkvsyal fqvddvnqpf einaitgeir  301 lrkaldfeei qsydvdveat dggglsgkcs lvvrvldvnd napeltmsff islipenlpe  361 itvavfsvsd adsghnqqvi csiennlpfl lrpsvenfyt lvtegaldre sraeynitit  421 vtdlgtprlk tqqsitvqvs dvndnapaft qtsytlfvre nnspalhigs vsatdrdsgi  481 naqvtysllp pqdphlplss lvsinadngh lfalrsldye alqsfefrvg atdrgspals  541 sealvrllvl dandnspfvl yplqngsapc telvpraaep gylvtkvvav dgdsgqnawl  601 syqllkatep glfgvwahng evrtarllse rdaakqrlvv lvkdngeppr satatlhvll  661 vdgfsqpylp lpeaapaqaq adsltvylvv alasvsslfl fsvllfvavr lcrrsraasv  721 grysvpegpf pghlvdvsgt gtlsqsyqyk vcltggsetn efkflkpimp nfppqgtere  781 meetptsrns fpfs

An exemplary human PCDHB6 nucleic acid sequence is set forth below (SEQ ID NO: 70; GenBank Accession No: AF217752.1, Version 1, incorporated herein by reference):

   1 atgatgcaaa ctaaagtaca gaacaagaaa aggcaagtgg ctttcttcat tttattgatg   61 ctttggggag aggtgggttc tgaatcgatt cagtattccg tattggagga gacagaaagt  121 ggcacgtttg tggccaactt gacaaaggac ctgggactga gggtggggga gctggcttcg  181 cggggcgctc gggttgtttt caaagggaac agacaacatt tgcagtttga tccacagacc  241 catgatttac tgctaaatga aaaactggac cgggaggagc tgtgtggctc cactgagccg  301 tgtgtgctac ctttccaagt gttactggaa aaccccttgc agttttttca ggcttccttg  361 cgagtcagag atataaatga ccacgccccg gaattccctg ccagagaaat gctcctgaaa  421 atatcagaaa ttactatgcc aggaaagata tttcctttga aaatggcaca cgatttagac  481 accggcagca acggccttca gaggtacaca atcagctcca accctcactt ccacgttctc  541 acccgcaatc gcagcgaagg caggaagttc ccggagctgg tgctagacaa accgttggac  601 cgcgaggagc agccccaact caggctaacg ctgatcgcgc tggatggcgg gtctccgccc  661 cggtcaggga cctccgagat tcagatccag gttttggaca tcaatgacaa cgtccccgag  721 tttgctcagg agctctatga agcacaagtc cctgagaaca accccctcgg ctctctggtt  781 attaccgtct cagccagaga tttagatgca ggatcgtttg ggaaggtatc ttacgccctg  841 tttcaagtcg atgacgtcaa ccaacccttc gaaataaacg caatcacagg agaaattcgg  901 ctgagaaagg ctttggattt tgaggaaatt cagtcttatg acgtggatgt tgaggctaca  961 gatggtggag gcctatcagg aaaatgctct ttagtcgtca gggtcctgga cgtgaatgac 1021 aatgcccctg aactcaccat gtcgttcttc atcagcctca tcccagaaaa cttaccagag 1081 atcacagtgg cagttttcag tgtttcagat gcagactctg gacataacca acaggttatt 1141 tgttcaatag agaacaatct cccctttcta ctaagacctt ccgtggagaa tttctacacc 1201 ctggtaacag aaggcgcgct ggacagagag agcagagccg agtacaacat cactatcacg 1261 gtcactgatt tggggacacc aaggctgaaa acccagcaga gcataactgt gcaggtctcc 1321 gacgtcaatg acaacgtccc cgccttcacc caaacctcct acaccctgtt cgtccgcgag 1381 aacaacagcc ccgccctgca catcggcagc gtcagcgcca cagacagaga ctcaggcatc 1441 aacgcccagg tcacctactc gctgctgccg ccccaggacc cgcacctgcc cctctcttcc 1501 ctggtctcca tcaacgcgga caacggccac ctgtttgccc tcaggtcgct ggactacgag 1561 gccctgcagt ctttcgagtt ccgcgtgggc gccacagacc gcggctcccc ggcgttgagc 1621 agcgaggcgc tggtgcgctt gctggtgctg gacgccaacg acaactcgcc cttcgtgttg 1681 tacccgctgc agaacggctc cgcgccctgc accgagctgg tgccccgggc ggccgagccg 1741 ggctacctgg tgaccaaggt ggtggcggtg gacggcgact cgggccagaa cgcctggctg 1801 tcgtaccagc tgctcaaggc cacggagctc ggtctgttcg gcgtgtgggc gcacaatggc 1861 gaggtgcgca ccgccaggct gctgagcgag cgagacgcag ccaagcacag gctggtggtg 1921 cttgtcaagg acaatggcga gcctccgcgc tcggccaccg ccacgctgca cgtgctcctg 1981 gtggacggct tctcccagcc ctacctgcct ctccctgagg cggccccggc ccaagcccag 2041 gccgactctc tcaccgtcta cctggtggtg gcgttggcct cggtgtcgtc gctcttcctc 2101 ttttcggtgc tcctgttcgt ggcggtgcgg ctgtgcagga ggagcagggc ggcctcggtg 2161 ggtcgctact cggtgcccga gggtcccttt ccagggcatc tggtggatgt gagcggcacc 2221 gggaccctat cccagagcta ccagtacaag gtgtgtctga cgggaggctc agaaacaaat 2281 gagttcaagt tcctgaagcc gattatgccc aacttccctc ctcagggcac tgagagagaa 2341 atggaagaaa cccccacctc tcggaatagc ttcccgttca gttaagtgtg ggattatttt 2401 actaaatctt acttatgttt ggagatctct tttaacttaa agttacatgg tctgtttctt 2461 gtttatttta cctctattct ttaggttgaa attttatata aagtaagata ctggtatctt 2521 agtatttcct gttcatgctt agtagtttat tacttcactt gagggtactt gacaatatga 2581 acaaaaagta aatttttatt tgcataattt taagcttttg aaattaaatt atctattctt 2641 ccccccccca aaaaaaagta ttgtaaatcc ttaagtaaaa ttgtatttct agctattggt 2701 aagagttgtt tcactattgc tatgtaggac tgtttaaaat gtgagtatct gatattattt 2761 aatcctccaa tgtctcattt tgcagtaact cctacagtgt gtaacactaa aaataagaac 2821 taatgatggc taaacactaa agtagccatt catacttatg catattttag tatcccataa 2881 tagtcaatcc aaaatttttg tgactataga ctttactgaa gtgtcaacac attagtttgt 2941 gagcctcatg taagaacatg atggtctttt tttaaaaaaa aagtcgtgcc aattataagt 3001 gcttaataaa tatttgctga atgttactaa

An exemplary human PCDHB10 amino acid sequence is set forth below (SEQ ID NO: 71; GenBank Accession No: AAQ89082.1, Version 1, incorporated herein by reference):

   1 mavrelcfpr qrqvlflflf wgvslagsgf grysvteete kgsfvvnlak dlglaegela   61 argtrvvsdd nkqyllldsh tgnlltnekl dreklcgpke pcmlyfqilm ddpfqiyrae  121 lrvrdindha pvfqdketvl kisentaegt afrleraqdp dgglngiqny tispnsffhi  181 nisggdegmi ypelvldkal dreeqgelsl tltaldggsp srsgtstvri vvldvndnap  241 qfaqalyetq apenspigfl ivkvwaedvd sgvnaevsys ffdasenirt tfqinpfsge  301 iflrelldye lvnsykiniq amdggglsar crvlvevldt ndnppelivs sfsnsvaens  361 petplavfki ndrdsgengk mvcyiqenlp fllkpsvenf yilitegald reiraeynit  421 itvtdlgtpr lktehnitvl vsdvndnapa ftqtsytlfv rennspalhi gsvsatdrds  481 gtnaqvtysl lppqdphlpl aslvsinadn ghlfalrsld yealqafefr vgatdrgspa  541 lsrealvrvl vldandnspf vlyplqngsa pctelvpraa epgylvtkvv avdgdsgqna  601 wlsyqllkat epglfgvwah ngevrtarll serdaakhrl vvlvkdngep prsatatlhl  661 llvdgfsqpy lplpeaapaq aqaeadlltv ylvvalasvs slfllsvllf vavrlcrrsr  721 aasvgrcsvp egpfpghlvd vrgaetlsqs yqyevcltgg pgtsefkflk pvisdiqaqg  781 pgrkgeenst frnsfgfniq

An exemplary human PCDHB10 nucleic acid sequence is set forth below (SEQ ID NO: 72; GenBank Accession No: NM_018930.3, Version 3, incorporated herein by reference):

   1 gaagacacgg acagatgaac ttaaaagaga agctttagct gccaaagatt gggaaaggga   61 aaggacaaaa aagacccctg ggctacacgg cgtaggtgca gggtttccta ctgctgttct  121 tttatgctgg gagctgtggc tgtaaccaac taggaaataa cgtatgcagc agctatggct  181 gtcagagagt tgtgcttccc aagacaaagg caagtcctgt ttctttttct tttttgggga  241 gtgtccttgg caggttctgg gtttggacgt tattcggtga ctgaggaaac agagaaagga  301 tcctttgtgg tcaatctggc aaaggatctg ggactagcag agggggagct ggctgcaagg  361 ggaaccaggg tggtttccga tgataacaaa caatacctgc tcctggattc acataccggg  421 aatttgctca caaatgagaa actggaccga gagaagctgt gtggccctaa agagccctgt  481 atgctgtatt tccaaatttt aatggatgat ccctttcaga tttaccgggc tgagctgaga  541 gtcagggata taaatgatca cgcgccagta tttcaggaca aagaaacagt cttaaaaata  601 tcagaaaata cagctgaagg gacagcattt agactagaaa gagcacagga tccagatgga  661 ggacttaacg gtatccaaaa ctacacgatc agccccaact cttttttcca tattaacatt  721 agtggcggtg atgaaggcat gatatatcca gagctagtgt tggacaaagc actggatcgg  781 gaggagcagg gagagctcag cttaaccctc acagcgctgg atggtgggtc tccatccagg  841 tctgggacct ctactgtacg catcgttgtc ttggacgtca atgacaatgc cccacagttt  901 gcccaggctc tgtatgagac ccaggctcca gaaaacagcc ccattgggtt ccttattgtt  961 aaggtatggg cagaagatgt agactctgga gtcaacgcgg aagtatccta ttcatttttt 1021 gatgcctcag aaaatattcg aacaaccttt caaatcaatc ctttttctgg ggaaatcttt 1081 ctcagagaat tgcttgatta tgagttagta aattcttaca aaataaatat acaggcaatg 1141 gacggtggag gcctttctgc aagatgtagg gttttagtgg aagtattgga caccaatgac 1201 aatccccctg aactgatcgt atcatcattt tccaactctg ttgctgagaa ttctcctgag 1261 acgccgctgg ctgtttttaa gattaatgac agagactctg gagaaaatgg aaagatggtt 1321 tgctacattc aagagaatct gccattccta ctaaaacctt ctgtggagaa tttttacatc 1381 ctaattacag aaggcgcgct ggacagagag atcagagccg agtacaacat cactatcacc 1441 gtcactgact tggggacacc caggctgaaa accgagcaca acataacggt cctggtctcc 1501 gacgtcaatg acaacgcccc cgccttcacc caaacctcct acaccctgtt cgtccgcgag 1561 aacaacagcc ccgccctgca catcggcagc gtcagcgcca cagacagaga ctcgggcacc 1621 aacgcccagg tcacctactc gctgctgccg ccccaagacc cgcacctgcc cctcgcctcc 1681 ctggtctcca tcaacgcgga caacggccac ctgttcgccc tcaggtcgct ggactacgag 1741 gccctgcagg ctttcgagtt ccgcgtgggc gccacagacc gcggctcccc cgcgctgagc 1801 agagaggcgc tggtgcgcgt gctggtgctg gacgccaacg acaactcgcc cttcgtgctg 1861 tacccgctgc agaacggctc cgcgccctgc accgagctgg tgccccgggc ggccgagccg 1921 ggctacctgg tgaccaaggt ggtggcggtg gacggcgact cgggccagaa cgcctggctg 1981 tcgtaccagc tgctcaaggc cacggagccc gggctgttcg gtgtgtgggc gcacaatggg 2041 gaggtgcgca ccgccaggct gctgagcgag cgcgacgcag ccaagcacag gctcgtggtg 2101 cttgtcaagg acaatggcga gcctcctcgc tcggccaccg ccacgctgca cttgctcctg 2161 gtggacggct tctcccagcc ctacctgcct ctcccggagg cggccccggc ccaggcccag 2221 gccgaggccg acttgctcac cgtctacctg gtggtggcgt tggcctcggt gtcttcgctc 2281 ttcctcctct cggtgctcct gttcgtggcg gtgcggctgt gcaggaggag cagggcggcc 2341 tcggtgggtc gctgctcggt gcccgagggt ccttttccag ggcatctggt ggacgtgagg 2401 ggcgctgaga ccctgtccca gagctaccag tatgaggtgt gtctgacggg aggccccggg 2461 accagtgagt tcaagttctt gaaaccagtt atttcggata ttcaggcaca gggccctggg 2521 aggaagggtg aagaaaattc caccttccga aatagctttg gatttaatat tcagtaaagt 2581 ctgtttttag tttcatatac ttttggtgtg ttacatagcc atgtttctat tagtttactt 2641 ttaaatctca aatttaagtt attatgcaac ttcaagcatt attttcaagt agtatacccc 2701 tgtggtttta caatgtttca tcattttttt gcattaataa caactgggtt taatttaatg 2761 agtatttttt tctaaatgat agtgttaagg ttttaattct ttccaactgc ccaaggaatt 2821 aattactatt atatctcatt acagaaatct gaggttttga ttcatttcag agcttgcatc 2881 tcatgattct aatcacttct gtctatagtg tacttgctct atttaagaag gcatatctac 2941 atttccaaac tcattctaac attctatata ttcgtgtttg aaaaccatgt catttatttc 3001 tacatcatgt atttaaaaag aaatatttct ctactactat gctcatgaca aaatgaaaca 3061 aagcatattg tgagcaatac tgaacatcaa taataccctt agtttatata cttattattt 3121 tatctttaag catgctactt ttacttggcc aatattttct tatgttaact tttgctgatg 3181 tataaaacag actatgcctt ataattgaaa taaaattata atctgcctga aaatgaataa 3241 aaataaaaca ttttgaaatg tgaaaaaaaa aaaaaaaaaa aaaa

An exemplary human PCDHGA3 amino acid sequence is set forth below (SEQ ID NO: 73; GenBank Accession No: Q9Y5H0.2, Version 2, incorporated herein by reference):

   1 mtnclsfrng rglallcall gtlcetgsgq irysvseeld kgsfvgnian dlgleprela   61 ergvrivsrg rtqlfslnpq sgslvtaeri dreelcaqip lclvkinilv edklkifeve  121 ieikdindna pnfpteelei kigeltvpgt rfpiktafdp dvginslqny klspndyfsl  181 avnsysegak ypelvleral drekkeihql vlvasdggdp vhsgnlhiqv ivldandnpp  241 mftqpeyrvs vwenvpvgtr lltvnatdpd egfnaqvsyi ldkmpgkiae ifhlnsvsge  301 vsilksldye damfyeikie aqdgpgllsr akilvtvldv ndnapeitit sltssvpeeg  361 tvgreialid vhdrdsgqng gvevfvlgnl pfkleksidq yyrlvtatsl dreqiseyni  421 slrasdggsp plstethitl hvidindnpp tfphlsysay ipennprgas ifsvtaqdpd  481 snnnaritya ltedtlqgap lssfvsinsn tgvlyalrsf dyeqfrdlkl lvtasdsgnp  541 plssnvslnl fvldqndnap eilypalptd gstgvelapr saepgylvtk vvavdrdsgq  601 nawlsyrllk asepglfsvg lhtgevrtar alldrdalkq slvvavqdhg qpplsatvtl  661 tvavadripd iladlgslep sakpndsdlt lylvvavaav scvflafviv llalrlrrwh  721 ksrllqasgg glastpgshf vgadgvrafl qtyshevslt adsrkshlif pqpnyadtli  781 sqesceksep llitqdllem kgdsnllqqa ppntdwrfsq aqrpgtsgsq ngddtgtwpn  841 nqfdtemlqa milasaseaa dgsstlggga gtmglsaryg pqftlqhvpd yrqnvyipgs  901 natltnaagk rdgkapaggn gnkkksgkke kk

An exemplary human PCDHGA3 nucleic acid sequence is set forth below (SEQ ID NO: 74; GenBank Accession No: NM_018916.3, Version 3, incorporated herein by reference):

   1 atgaccaatt gcctgagttt ccgaaatggc agaggactgg ccctgctgtg cgcgctcctg   61 gggacgctgt gcgaaacagg atccggtcag atccgctact cggtgtctga ggagctagat  121 aaaggttcct tcgtgggcaa catcgctaac gacctggggc tagagccccg ggagctggcg  181 gagcgcggag tccgcatcgt ctccagaggt aggacgcagc ttttctctct gaatccgcaa  241 agcggcagct tggtcaccgc ggagaggata gaccgggagg agctctgcgc tcagatcccg  301 ctgtgtctgg taaaaattaa cattctggtt gaggataaat tgaaaatttt tgaagtagaa  361 atagaaatta aagatattaa tgataatgct cctaatttcc caacagagga attggaaata  421 aaaattggtg aactaacggt tcctggaacc cgatttccaa ttaaaactgc ttttgaccca  481 gatgtaggca ttaactccct gcagaactac aagcttagcc ccaatgacta cttctctctg  541 gctgtgaata gcgtctctga gggggccaag tatccagagc tggtgctgga gcgggccctg  601 gaccgtgaga aaaaagaaat tcaccagctt gtcctggttg cctctgatgg tggcgaccct  661 gtccactctg gcaacttgca catccaagtg atagtcctgg atgcaaatga caacccacca  721 atgtttactc agcctgagta ccgtgtgagt gtttgggaga acgtgcctgt gggtacccgg  781 ctgctcacgg tgaatgccac tgaccctgac gagggattca atgctcaagt gtcttatatt  841 ctagataaaa tgcctgggaa aatcgctgag attttccatc ttaactcagt gagtggagaa  901 gtatcaatat taaaaagtct agattatgag gatgccatgt tctatgaaat taaaattgaa  961 gcacaggatg gaccaggtct tctttcaaga gccaagattc tagtcacggt tctggatgtg 1021 aatgacaatg ctccagaaat tacaatcacg tctctcacaa gctcagtccc agaagagggc 1081 accgttggaa gagaaattgc tcttatcgac gtgcatgacc gagattctgg gcagaatggg 1141 caggttgaag tttttgtcct gggaaatctg ccatttaagt tagaaaaatc aatagatcaa 1201 tattaccgct tagtgacggc cacatccctg gaccgcgaac aaatatcaga atataacatt 1261 agtctgagag cctcagatgg gggaagcccg ccactgtcca cagaaactca catcaccctg 1321 catgtgattg acatcaatga caacccaccc accttccctc atttatccta ctccgcctac 1381 attccagaaa acaaccccag aggagcctcc atcttctcag tgacagccca ggacccagat 1441 agcaacaaca acgcccgcat cacttatgca ttgaccgagg acactctcca gggggcgccc 1501 ctgtcctcct tcgtctctat caactccaac actggcgtcc tatacgcgct gagatccttc 1561 gactacgagc aatttagaga cttaaagcta ctggtgacag ccagcgacag cgggaaccct 1621 ccactcagca gcaacgtgtc gctgaacctg ttcgtgctgg accagaacga caacgcgccc 1681 gagatcctgt accccgccct ccccacagac ggttccactg gcgtggagct ggcgcctcgc 1741 tccgcagagc ccggctacct ggtgaccaag gtggtggcgg tggacagaga ctcgggccag 1801 aacgcctggc tgtcctaccg cctgctcaag gccagcgagc cgggactctt ctcggtgggt 1861 ctgcacacgg gcgaggtgcg cacggcgcga gccctgctgg acagagacgc gctcaagcag 1921 agcctcgtgg tggccgtcca ggaccacggc cagccccctc tctccgccac tgtcacgctc 1981 accgtggccg tggccgacag gatccccgac atcctggccg acctgggcag cctcgagccc 2041 tccgccaaac ccaacgattc ggacctcact ctgtacctgg tggtggcggt ggccgcggtc 2101 tcctgcgtct tcctggcctt cgtcatcgtg ctgctggcgc tcaggctgcg gcgctggcac 2161 aagtcacgcc tgctgcaggc ttcgggaggc ggcttggcga gtacgcccgg ctcgcacttt 2221 gtgggcgcgg acggggttcg ggctttcctg cagacctatt cccacgaggt ctccctcact 2281 gcggactcgc ggaagagcca cctgattttc ccccagccca actatgcgga cacgctcatc 2341 agccaggaga gctgtgagaa aagcgagcct cttctgataa ctcaggattt acttgaaatg 2401 aaaggagatt ccaacctact tcagcaagcc ccgcccaaca cggactggcg tttctctcag 2461 gcccagagac ccggcaccag cggctcccaa aatggcgatg acaccggcac ctggcccaac 2521 aaccagtttg acacagagat gctgcaagcc atgatcttgg cgtccgccag tgaagctgct 2581 gatgggagct ccaccctggg agggggtgcc ggcaccatgg gattgagcgc ccgctacgga 2641 ccccagttca ccctgcagca cgtgcccgac taccgccaga atgtctacat cccaggcagc 2701 aatgccacac tgaccaacgc agctggcaag cgggatggca aggccccagc aggtggcaat 2761 ggcaacaaga agaagtcggg caagaaggag aagaagtaac atggaggcca ggccaagagc 2821 cacagggcgg cctctcccca accagcccag cttctcctta cctgcaccca ggcctcagag 2881 tttcagggct aacccccaga atactggtag gggccaaggc catgctcccc ttgggaaaca 2941 gaaacaagtg cccagtcagc acctacccct tcccccccag ggggttgaat atgcaaaagc 3001 agttccgctg ggaaccccca tccaatcaac tgctgtaccc atgggggtag tggggttact 3061 gtagacacca agaaccattt gccacacccc gtttagttac agctgaactc ctccatcttc 3121 caaatcaatc aggcccatcc atcccatgcc tccctcctcc ccaccccact ccaacagttc 3181 ctctttcccg agtaaggtgg ttggggtgtt gaagtaccaa gtaacctaca agcctcctag 3241 ttctgaaaag ttggaagggc atcatgacct cttggcctct cctttgattc tcaatcttcc 3301 cccaaagcat ggtttggtgc cagccccttc acctccttcc agagcccaag atcaatgctc 3361 aagttttgga ggacatgatc accatcccca tggtactgat gcttgctgga tttagggagg 3421 gcattttgct accaagcctc ttcccaacgc cctggggacc agtcttctgt tttgtttttc 3481 attgtttgac gtttccactg catgccttga cttcccccac ctcctcctca aacaagagac 3541 tccactgcat gttccaagac agtatggggt ggtaagataa ggaagggaag tgtgtggatg 3601 tggatggtgg gggcatggac aaagcttgac acatcaagtt atcaaggcct tggaggaggc 3661 tctgtatgtc ctcaggggac tgacaacatc ctccagattc cagccataaa ccaataacta 3721 ggctggaccc ttcccactac ataatagggc tcagcccagg cagccagctt tgggctgagc 3781 taacaggacc aatggattaa actggcattt cagtccaagg aagctcgaag caggtttagg 3841 accaggtccc cttgagaggt cagaggggcc tctgtgggtg ctgggtactc cagaggtgcc 3901 actggtggaa gggtcagcgg agccccagca ggaagggtgg gccagccagg ccattcttag 3961 tccctgggtt ggggaggcag ggagctaggg cagggaccaa atgaacagaa agtctcagcc 4021 caggatgggg cttcttcaac agggcccctg ccctcctgaa gcctcagtcc ttcaccttgc 4081 caggtgccgt ttctcttccg tgaaggccac tgcccaggtc cccagtgcgc cccctagtgg 4141 ccatagcctg gttaaagttc cccagtgcct ccttgtgcat agaccttctt ctcccacccc 4201 cttctgcccc tgggtccccg gccatccagc ggggctgcca gagaacccca gacctgccct 4261 tacagtagtg tagcgccccc tccctctttc ggctggtgta gaatagccag tagtgtagtg 4321 cggtgtgctt ttacgtgatg gcgggtgggc agcgggcggc gggctccgcg cagccgtctg 4381 tccttgatct gcccgcggcg gcccgtgttg tgttttgtgc tgtgtccacg cgctaaggcg 4441 accccctccc ccgtactgac ttctcctata agcgcttctc ttcgcatagt cacgtagctc 4501 ccaccccacc ctcttcctgt gtctcacgca agttttatac tctaatattt atatggcttt 4561 ttttcttcga caaaaaaata ataaaacgtt tcttctgaaa agctg

An exemplary human PCDHGB1 amino acid sequence is set forth below (SEQ ID NO: 75; GenBank Accession No: AAI03929.1, Version 1, incorporated herein by reference):

   1 mqrareaemm ksqvlfpfll slfcgaisqq irytipeela ngsrvgklak dlglsvrelp   61 trklrvsaed yfnvslesgd llvngridre kicgrkleca lefetvaenp mnvfhvvvvi  121 qdindnaprf vakgidleic esalpgvkfs ldsaqdadve gnslklytin pnqyfslstk  181 espdgskypv lllekpldre hqsshrlilt amdggdppls gtthiwirvt dandnapvfs  241 qevyrvslqe nvpwgtsvlr vmatdqdegi naeityafln spistslfnl npntgdittn  301 gtldfeetsr yvlsveakdg gvhtahcnvq ieivdendna pevtfmsfsn qipedsdlgt  361 vialikvrdk dsgqngmvtc ytqeevpfkl estsknyykl viagalnreq tadynvtiia  421 tdkgkpalss rtsitlhisd indnapvfhq asyvvhvsen nppgasiaqv sasdpdlgpn  481 drvsysilas dleprellsy vsvspqsgvv faqrafdheq lrafeltlqa rdqgspalsa  541 nvslrvlvgd lndnaprvly palgpdgsal fdmvpraaep gylvtkvvav dadsghnawl  601 syhvlqasep glfslglrtg evrtaralgd rdaarqrllv avrdggqppl satatlhlif  661 adslqevlpd lsdrpepsdp qtelqfylvv alalisvlfl lavilaialr lrrsssldte  721 gcfqtglcsk sgpgvppnhs egtlpysynl ciashsakte fnslnltpem appqdllcdd  781 psmvvcasne dhkiaydpsl pshvsfckss

An exemplary human PCDHGB1 nucleic acid sequence is set forth below (SEQ ID NO: 76; GenBank Accession No: NM_018922.2, Version 2, incorporated herein by reference):

   1 atgcagagag ccagagaagc cgaaatgatg aaaagtcagg tactgtttcc cttcctgctg   61 tctttgttct gcggggccat ctcccagcag atccgataca cgattccaga ggagctagcc  121 aacggctcac gggtggggaa acttgccaag gatctggggc tcagtgtccg ggagttgcca  181 actcgaaaac tgcgggttag tgcagaggat tatttcaacg ttagtttgga gagcggggat  241 ttgttagtga acggtaggat agatcgagag aagatttgcg gaaggaaact tgagtgtgca  301 ctagaattcg aaacggtcgc tgaaaaccca atgaatgttt tccacgtggt tgttgtaatc  361 caagatatta atgacaatgc accacgtttc gttgcaaaag gcattgactt agaaatttgt  421 gagtcagcct tacccggggt aaaattctct ctggattctg ctcaagatgc agatgtggaa  481 ggcaattcac tgaagttata caccatcaac cccaatcaat acttctctct gtcaacgaag  541 gaaagtcctg atggaagtaa atatccggta ttactgctgg aaaaacctct agacagggaa  601 catcagagct ctcatcgctt aatcctgact gccatggatg gcggggaccc gcctctaagc  661 ggcaccaccc atatctggat ccgagttacg gatgccaatg ataatgctcc cgtgtttagc  721 caggaggtat acagggttag cctccaagaa aacgtaccgt ggggaacctc cgtgctgcgg  781 gtgatggcca cagaccagga tgagggcatt aatgcagaga tcacctatgc cttcctcaat  841 tccccaataa gtaccagcct cttcaatctc aatccaaata ctggcgacat cacaaccaat  901 ggcacattgg attttgaaga gacaagtaga tatgtgttga gtgtggaagc taaggatgga  961 ggagtacaca cagctcactg taatgttcaa atagaaattg ttgacgagaa tgacaatgcc 1021 ccagaggtga cattcatgtc cttctctaac cagattccag aggattcaga ccttggaact 1081 gtaatagccc tcataaaagt gcgagacaag gattctgggc aaaatggcat ggtgacatgc 1141 tatactcagg aagaagttcc tttcaaatta gaatccacct cgaagaatta ttacaagctg 1201 gtgattgctg gagccctaaa ccgggagcag acagcagact acaacgtcac aatcatagcc 1261 accgacaagg gcaaaccagc cctttcctcc aggacaagca tcaccctgca catctccgac 1321 atcaacgaca atgcacctgt tttccatcag gcctcctatg tggtccacgt gtctgagaac 1381 aacccacctg gcgcctccat tgcacaagta agcgcctccg acccggattt gggacccaac 1441 ggcagagtct cctactctat tctggccagt gacctggagc cgcgggagct gttgtcctac 1501 gtgtccgtga gcccgcagag cggggtggtg ttcgcgcagc gcgccttcga ccacgagcag 1561 ctgcgcgcct tcgagctcac actgcaggcc agggaccagg gctcccccgc gctcagcgcc 1621 aacgtgagcc tgcgcgtgtt ggtgggcgac ctcaatgaca atgcgccacg ggtgctgtac 1681 cccgcgctgg ggcctgatgg ctccgccctc ttcgatatgg tgccacgcgc cgcagagccc 1741 ggctacctgg tgaccaaggt ggtggcggtg gacgcagact caggacacaa cgcttggctg 1801 tcctaccacg tgctgcaggc cagcgagccc gggctcttca gcctggggtt gcgcacgggt 1861 gaggtgcgca cagcgcgtgc cttgggcgac agggacgcgg cccgccagcg cctgctggtc 1921 gctgtgcgtg atggaggaca gccgccactc tccgccaccg ccacgctgca cctaatcttc 1981 gcggatagcc tgcaagaggt attgccagac ctcagcgacc gccctgagcc ctctgacccc 2041 cagacggaac tgcagtttta cctggttgtg gccttggcct tgatctcagt gctctttctc 2101 ctcgcggtga ttctagcgat cgccctgcgc ctgcgacgtt cctccagcct cgacactgag 2161 ggctgctttc aaaccggtct ctgctccaag tctgggcccg gggttcctcc caaccacagc 2221 gaggggactt tgccctattc ctacaatcta tgtattgcct ctcattctgc aaagacagag 2281 tttaattctc tcaacctgac accggaaatg gctccccctc aggatctgct gtgtgatgat 2341 ccttctatgg ttgtatgtgc cagtaatgaa gatcacaaaa tcgcttatga cccttctttg 2401 tcttcgcacc aagccccgcc caacacggac tggcgtttct ctcaggccca gagacccggc 2461 accagcggct cccaaaatgg cgatgacacc ggcacctggc ccaacaacca gtttgacaca 2521 gagatgctgc aagccatgat cttggcgtcc gccagtgaag ctgctgatgg gagctccacc 2581 ctgggagggg gtgccggcac catgggattg agcgcccgct acggacccca gttcaccctg 2641 cagcacgtgc ccgactaccg ccagaatgtc tacatcccag gcagcaatgc cacactgacc 2701 aacgcagctg gcaagcggga tggcaaggcc ccagcaggtg gcaatggcaa caagaagaag 2761 tcgggcaaga aggagaagaa gtaacatgga ggccaggcca agagccacag ggcggcctct 2821 ccccaaccag cccagcttct ccttacctgc acccaggcct cagagtttca gggctaaccc 2881 ccagaatact ggtaggggcc aaggccatgc tccccttggg aaacagaaac aagtgcccag 2941 tcagcaccta ccccttcccc cccagggggt tgaatatgca aaagcagttc cgctgggaac 3001 ccccatccaa tcaactgctg tacccatggg ggtagtgggg ttactgtaga caccaagaac 3061 catttgccac accccgttta gttacagctg aactcctcca tcttccaaat caatcaggcc 3121 catccatccc atgcctccct cctccccacc ccactccaac agttcctctt tcccgagtaa 3181 ggtggttggg gtgttgaagt accaagtaac ctacaagcct cctagttctg aaaagttgga 3241 agggcatcat gacctcttgg cctctccttt gattctcaat cttcccccaa agcatggttt 3301 ggtgccagcc ccttcacctc cttccagagc ccaagatcaa tgctcaagtt ttggaggaca 3361 tgatcaccat ccccatggta ctgatgcttg ctggatttag ggagggcatt ttgctaccaa 3421 gcctcttccc aacgccctgg ggaccagtct tctgttttgt ttttcattgt ttgacgtttc 3481 cactgcatgc cttgacttcc cccacctcct cctcaaacaa gagactccac tgcatgttcc 3541 aagacagtat ggggtggtaa gataaggaag ggaagtgtgt ggatgtggat ggtgggggca 3601 tggacaaagc ttgacacatc aagttatcaa ggccttggag gaggctctgt atgtcctcag 3661 gggactgaca acatcctcca gattccagcc ataaaccaat aactaggctg gacccttccc 3721 actacataat agggctcagc ccaggcagcc agctttgggc tgagctaaca ggaccaatgg 3781 attaaactgg catttcagtc caaggaagct cgaagcaggt ttaggaccag gtccccttga 3841 gaggtcagag gggcctctgt gggtgctggg tactccagag gtgccactgg tggaagggtc 3901 agcggagccc cagcaggaag ggtgggccag ccaggccatt cttagtccct gggttgggga 3961 ggcagggagc tagggcaggg accaaatgaa cagaaagtct cagcccagga tggggcttct 4021 tcaacagggc ccctgccctc ctgaagcctc agtccttcac cttgccaggt gccgtttctc 4081 ttccgtgaag gccactgccc aggtccccag tgcgccccct agtggccata gcctggttaa 4141 agttccccag tgcctccttg tgcatagacc ttcttctccc acccccttct gcccctgggt 4201 ccccggccat ccagcggggc tgccagagaa ccccagacct gcccttacag tagtgtagcg 4261 ccccctccct ctttcggctg gtgtagaata gccagtagtg tagtgcggtg tgcttttacg 4321 tgatggcggg tgggcagcgg gcggcgggct ccgcgcagcc gtctgtcctt gatctgcccg 4381 cggcggcccg tgttgtgttt tgtgctgtgt ccacgcgcta aggcgacccc ctcccccgta 4441 ctgacttctc ctataagcgc ttctcttcgc atagtcacgt agctcccacc ccaccctctt 4501 cctgtgtctc acgcaagttt tatactctaa tatttatatg gctttttttc ttcgacaaaa 4561 aaataataaa acgtttcttc tgaaaagctg

An exemplary human PCDHGB2 amino acid sequence is set forth below (SEQ ID NO: 77; GenBank Accession No: AAI01806.1, Version 1, incorporated herein by reference):

   1 mkassgrcgl vrwlqvllpf llslfpgalp vqirysipee laknsvvgnl akdlglsvrd   61 lparklrvsa ekeyftvnpe sgdllvsdri dreqicgkqp lcvldfdtva enplnifyia  121 vivqdindnt plfkqtkinl kigestkpgt tfpldpalds dvgpnslqry hlndneyfdl  181 aekqtpdgrk ypelilkhsl dreehslhql vltavdggdp pgsgttqiri kvtdandnpp  241 vfsqdvyrvt lredvppgff vlqvtatdrd eginaeitys fhnvdeqvkh ffnlnektge  301 ittkddldfe iassytlsie akdpgdlaah csiqveildd ndcapevivt svstplpeds  361 ppgtvialik trdrdsgeng evycqvlgna kfilkssskn yyklvtdgal dreeipeynl  421 titatdggkp plsssiivtl hisdvndnap vfqqtsymvh vaennppgas iaqisasdpd  481 lgpsgqvsys ivasdlkpre ilsyvsvsaq sgvvfaqraf dheqlrafel tlqardqgsp  541 alsanvslrv lvgdlndnap rvlypalgpd gsalfdmvpr aaepgylvtk vvavdadsgh  601 nawlsyhvlq asepglfslg lrtgevrtar algdrdaarq rllvavrdgg qpplsatatl  661 hlifadslqe vlpdlsdrre psdpqaklqf ylvvalalis vlfflavila islrlrlssr  721 sdawdcfqpg lsskpgpgvl pnysegtlpy synlcvasqs aktefnflni tpelvpaqdl  781 vcdnasweqn tnhgaagvpf asdtilkvsf n

An exemplary human PCDHGB2 nucleic acid sequence is set forth below (SEQ ID NO: 78; GenBank Accession No: NM_018923.2, Version 2, incorporated herein by reference):

   1 atgaaagcga gctcagggag gtgcgggctg gtgcggtggc tgcaggtact gttgcccttc   61 ctgttgtctt tgttccccgg ggctctccca gtccagatcc gctattcaat tccagaggag  121 ctggccaaaa actcggtcgt aggaaacctc gccaaggatc tggggctcag cgtccgggac  181 ttgccagccc ggaagctgcg ggttagcgcg gagaaggaat atttcacagt aaacccagaa  241 agcggagact tacttgtgag tgacagaata gaccgagaac agatatgcgg gaagcagcct  301 ctgtgtgttc tggatttcga tactgtcgct gaaaatccac taaatatttt ctacatagca  361 gtaattgtgc aggatataaa tgataatacc ccgctattca aacagactaa gattaattta  421 aaaattggcg aatccactaa gccaggtaca acatttccac ttgacccagc cctggattca  481 gatgttggtc ctaactcact acaaagatac caccttaatg acaacgagta ctttgatctc  541 gctgagaaac agactccaga tggtcgtaaa tatcctgagt tgattctaaa acactctctg  601 gacagagaag agcacagttt acatcaattg gtcctcacag ctgtggatgg cggagaccca  661 cctcaaagtg gcacgaccca aatccgaatc aaagtcacgg atgccaacga taaccctcca  721 gtgttcagcc aggacgtgta cagggtcacc ctgagggagg acgtgccgcc gggcttcttt  781 gtgcttcaag tgacagccac cgaccgggat gaaggcataa acgcagagat cacctactcc  841 tttcataatg tggacgaaca agtgaaacac tttttcaact taaatgaaaa aacaggagaa  901 atcacgacaa aggatgattt ggattttgag attgcaagta gttacactct gagtatcgaa  961 gcaaaagatc ctggagatct agcagcccac tgcagtatcc aagttgaaat tcttgatgac 1021 aacgattgtg cacctgaagt tattgtgact tcagtatcta ctcccctacc ggaggattcg 1081 ccaccaggaa cagtgatcgc cttgataaaa acgagagaca gagactctgg agaaaatgga 1141 gaagtttact gccaagtgtt gggaaatgcc aagtttattt tgaaatcttc ctcaaagaac 1201 tattacaaac tagtgacaga cggcgctctg gaccgggagg agatcccaga atacaatctc 1261 accatcacag ccaccgacgg gggcaagccg cccctctcct ccagcataat tgtcaccctg 1321 cacatctccg acgtcaacga taatgcccca gttttccaac agacttccta catggttcac 1381 gtggcagaga acaatcctcc tggcgcctct atcgctcaaa tcagtgcctc tgaccctgac 1441 ttgggcccca gtggccaagt ttcctactcc atcgtagcga gcgacctgaa gccgcgggag 1501 attttatcct acgtgtccgt gagcgcgcag agcggggtgg tgttcgcgca gcgcgccttc 1561 gatcatgagc agctgcgcgc cttcgagctc acactgcagg cccgcgacca gggctcgccc 1621 gcgctcagcg ccaacgtgag cctgcgcgtg ttagtgggcg acctcaatga caatgcgcca 1681 cgggtgctgt accccgcgct ggggcctgat ggctccgccc tcttcgatat ggtgccacgc 1741 gccgcagagc ccggctacct ggtgaccaag gtggtggcgg tggacgcaga ctcaggacac 1801 aacgcttggc tgtcctacca cgtgctgcag gccagcgagc ccgggctctt cagcctgggg 1861 ttgcgcacgg gtgaggtgcg cacagcgcgt gccttgggcg acagggacgc ggcccgccag 1921 cgcctgctgg tcgctgtgcg tgatggagga cagccgccac tctccgctac ggccacgctg 1981 cacctaatct tcgcggatag cctgcaagag gtattgccag acctcagcga ccgccgggag 2041 ccctctgacc cccaggcaaa actgcagttt tacctggttg tggccttggc cttgatctca 2101 gtgctcttct tcctcgcggt gattctggca atctccctgc gcctgcgact ctcttccagg 2161 tcagatgctt gggactgttt tcagcctggt ctcagctcca agcctggacc tggggttctc 2221 cccaattaca gtgagggtac attgccctat tcctacaacc tgtgtgttgc ctcacaatca 2281 gccaagacag agttcaattt tctgaacata accccggaat tggttcccgc gcaagatctc 2341 gtctgtgaca atgcctcttg ggaacaaaat acaaatcatg gagccgctgg ggtccctttt 2401 gcctcagata ctattttgaa gcaagccccg cccaacacgg actggcgttt ctctcaggcc 2461 cagagacccg gcaccagcgg ctcccaaaat ggcgatgaca ccggcacctg gcccaacaac 2521 cagtttgaca cagagatgct gcaagccatg atcttggcgt ccgccagtga agctgctgat 2581 gggagctcca ccctgggagg gggtgccggc accatgggat tgagcgcccg ctacggaccc 2641 cagttcaccc tgcagcacgt gcccgactac cgccagaatg tctacatccc aggcagcaat 2701 gccacactga ccaacgcagc tggcaagcgg gatggcaagg ccccagcagg tggcaatggc 2761 aacaagaaga agtcgggcaa gaaggagaag aagtaacatg gaggccaggc caagagccac 2821 agggcggcct ctccccaacc agcccagctt ctccttacct gcacccaggc ctcagagttt 2881 cagggctaac ccccagaata ctggtagggg ccaaggccat gctccccttg ggaaacagaa 2941 acaagtgccc agtcagcacc taccccttcc cccccagggg gttgaatatg caaaagcagt 3001 tccgctggga acccccatcc aatcaactgc tgtacccatg ggggtagtgg ggttactgta 3061 gacaccaaga accatttgcc acaccccgtt tagttacagc tgaactcctc catcttccaa 3121 atcaatcagg cccatccatc ccatgcctcc ctcctcccca ccccactcca acagttcctc 3181 tttcccgagt aaggtggttg gggtgttgaa gtaccaagta acctacaagc ctcctagttc 3241 tgaaaagttg gaagggcatc atgacctctt ggcctctcct ttgattctca atcttccccc 3301 aaagcatggt ttggtgccag ccccttcacc tccttccaga gcccaagatc aatgctcaag 3361 ttttggagga catgatcacc atccccatgg tactgatgct tgctggattt agggagggca 3421 ttttgctacc aagcctcttc ccaacgccct ggggaccagt cttctgtttt gtttttcatt 3481 gtttgacgtt tccactgcat gccttgactt cccccacctc ctcctcaaac aagagactcc 3541 actgcatgtt ccaagacagt atggggtggt aagataagga agggaagtgt gtggatgtgg 3601 atggtggggg catggacaaa gcttgacaca tcaagttatc aaggccttgg aggaggctct 3661 gtatgtcctc aggggactga caacatcctc cagattccag ccataaacca ataactaggc 3721 tggacccttc ccactacata atagggctca gcccaggcag ccagctttgg gctgagctaa 3781 caggaccaat ggattaaact ggcatttcag tccaaggaag ctcgaagcag gtttaggacc 3841 aggtcccctt gagaggtcag aggggcctct gtgggtgctg ggtactccag aggtgccact 3901 ggtggaaggg tcagcggagc cccagcagga agggtgggcc agccaggcca ttcttagtcc 3961 ctgggttggg gaggcaggga gctagggcag ggaccaaatg aacagaaagt ctcagcccag 4021 gatggggctt cttcaacagg gcccctgccc tcctgaagcc tcagtccttc accttgccag 4081 gtgccgtttc tcttccgtga aggccactgc ccaggtcccc agtgcgcccc ctagtggcca 4141 tagcctggtt aaagttcccc agtgcctcct tgtgcataga ccttcttctc ccaccccctt 4201 ctgcccctgg gtccccggcc atccagcggg gctgccagag aaccccagac ctgcccttac 4261 agtagtgtag cgccccctcc ctctttcggc tggtgtagaa tagccagtag tgtagtgcgg 4321 tgtgctttta cgtgatggcg ggtgggcagc gggcggcggg ctccgcgcag ccgtctgtcc 4381 ttgatctgcc cgcggcggcc cgtgttgtgt tttgtgctgt gtccacgcgc taaggcgacc 4441 ccctcccccg tactgacttc tcctataagc gcttctcttc gcatagtcac gtagctccca 4501 ccccaccctc ttcctgtgtc tcacgcaagt tttatactct aatatttata tggctttttt 4561 tcttcgacaa aaaaataata aaacgtttct tctgaaaagc tg

An exemplary human EMILIN1 amino acid sequence is set forth below (SEQ ID NO: 79; GenBank Accession No: AAH07530.1, Version 1, incorporated herein by reference):

  1 madlgatkdr iiseinrlqq eatehatese erfrgleegq aqagqcpsle grlgrlegvc  61 erldtvaggl qglreglsrh vaglwaglre tnttsqmqaa lleklvggqa glgrrlgaln 121 sslqlledrl hqlslkdltg egtkgpagea gppgppglqg ppgpagppgs pgkdgqegpi 181 gppgpqgeqg vegapaapvp qvafsaalsl prsepgtvpf drvllndggy ydpetgvfta 241 plagryllsa vltghrhekv eavlsrsnqg varvdsggye peglenkpva esqpspgtlg 301 vfslilplqa gdtvcvdlvm gqlahseepl tifsgallyg dpeleha

An exemplary human EMILIN1 nucleic acid sequence is set forth below (SEQ ID NO: 80; GenBank Accession No: NM_007046.3, Version 3, incorporated herein by reference):

   1 gggaggggag ccagcaggga ggaggaggcc agggcccgcc ccacagccac tctcgcgcct   61 ccgaacagcc acaggggcaa agccctgtca cccccaggat ccggtcatca gggaaagagg  121 acagggagac cagaagaggg ccagctggga cgagggggcg gacgcccagg aggcaacttc  181 tgagacgcag ctcctgagag gggcagggac caggcgcggg aggccagagg gggcacagag  241 aacaaacccc ctcagaagtg aagaggagag cggaaggaac cgagagggga cggacaggag  301 ctgaggagga aagaggaggg gagaggggtc aggccaggca gccaaggaga agacgtgtgg  361 ccgggggcta tcagaaggaa actgggacgg acgggccggg ctcgggctgt cctgtggagc  421 agcagcatcc ccggggccgg cagaggcgcc agtggctggg cgggatgagt ctctgagggc  481 cactgtggag cgccccgcca tggccccccg caccctctgg agctgctacc tctgctgcct  541 gctgacggca gctgcagggg ccgccagcta ccctcctcga ggtttcagcc tctacacagg  601 ttccagtggg gccctcagcc ccggggggcc ccaggcccag attgcccccc ggccagccag  661 ccgccacagg aactggtgtg cctacgtggt gacccggaca gtgagctgtg tccttgagga  721 tggagtggag acatatgtca agtaccagcc ttgtgcctgg ggccagcccc agtgtcccca  781 aagcatcatg taccgccgct tcctccgccc tcgctaccgt gtggcctaca agacagtgac  841 cgacatggag tggaggtgct gtcagggtta tgggggcgat gactgtgctg agagtcccgc  901 tccagcgctg gggcctgcgt cttccacacc acggcccctg gcccggcctg cccgccccaa  961 cctctctggc tccagtgcag gcagccccct cagtggactg gggggagaag gtcctgggga 1021 gtcagagaag gtgcagcagc tggaggaaca ggtgcagagc ctgaccaagg agctgcaagg 1081 cctgcggggc gtcctgcaag gactgagcgg gcgcctggca gaggatgtgc agagggctgt 1141 ggagacggcc ttcaacggga ggcagcagcc agctgacgcg gctgcccgcc ctggggtgca 1201 tgaaaccctc aatgagatcc agcaccagct gcagctcctg gacacccgcg tctccaccca 1261 cgaccaggag ctgggtcacc tcaacaacca tcatggcggc agcagcagca gtgggggcag 1321 cagggcccca gccccagcct cagcccctcc gggccccagt gaggagctgc tgcggcagct 1381 ggagcagcgg ttgcaggagt cctgctccgt gtgcctggcc gggctagatg gcttccgccg 1441 gcagcagcag gaggacaggg agcggctgcg agcgatggag aagctgctgg cctcggtgga 1501 ggagcggcaa cggcacctcg cagggctggc ggtgggccgc aggccccctc aggaatgctg 1561 ctctccagag ctgggccggc gactggcaga gctggagcgc aggctggatg tcgtggccgg 1621 ctcagtgaca gtgctgagtg ggcggcgagg cacagagctg ggaggagccg cggggcaggg 1681 aggccacccc ccaggctaca ccagcttggc ctcccgcctg tctcgcctgg aggaccgctt 1741 caactccacc ctgggccctt cggaggagca ggaggagagc tggcctgggg ctcctggggg 1801 gctgagccac tggctgcctg ctgcccgggg ccgactagag cagttggggg ggctgctggc 1861 caatgtgagc ggggagctgg gggggcggtt ggatctgttg gaggagcagg tggcaggggc 1921 catgcaggca tgcgggcagc tctgctctgg ggcccctggg gagcaggact ctcaagtcag 1981 cgagatcctc agtgccttgg agcgcagggt gctggacagt gaggggcagc tgcggctggt 2041 gggctccggc ctgcacacgg tggaagcagc gggggaggcc cggcaggcca cgctggaggg 2101 attacaagag gttgtgggcc ggctccagga tcgtgtggat gcccaggatg agacagctgc 2161 agagttcaca ctacggctga atctcactgc ggcccggcta ggccaactgg aggggctgct 2221 gcaggcccat ggggatgagg gctgtggggc ctgtggcgga gtccaagagg aactaggccg 2281 ccttcgggat ggtgtggagc gctgctcctg ccccctgttg cctcctcggg gtcctggggc 2341 tggtccaggt gttgggggcc caagccgtgg gcccctggac ggcttcagcg tgtttggggg 2401 cagctcaggc tcagccctgc aggccctgca aggagagctc tctgaggtta ttctcagctt 2461 cagctccctc aatgactcac tgaatgagct ccagaccact gtggagggcc agggcgctga 2521 tctggctgac ctgggggcaa ccaaggaccg tatcatttct gagattaaca ggctgcagca 2581 ggaggccaca gagcatgcta cagagagtga agagcgcttc cgaggcctag aggagggaca 2641 agcacaggcc ggccagtgcc ccagcttaga ggggcgattg ggccgtcttg agggtgtctg 2701 tgaacggttg gacactgtgg ctgggggact gcagggcctg cgcgagggcc tttccagaca 2761 cgtggctggg ctctgggctg ggctccggga aaccaacacc accagccaga tgcaggcagc 2821 cctgctggag aagctggtcg ggggacaggc gggcctgggc aggcggctgg gtgcccttaa 2881 cagctccctg cagctcctgg aggaccgtct gcaccagctc agcctgaagg acctcactgg 2941 gcctgcagga gaggctgggc ccccagggcc tcctgggctg cagggacccc caggccctgc 3001 tggacctcca ggatcaccag gcaaggacgg gcaagagggc cccatcgggc caccaggtcc 3061 tcaaggtgaa cagggagtgg agggggcacc agcagcccct gtgccccaag tggcattttc 3121 agctgctctg agtttgcccc ggtctgaacc aggcacggtc cccttcgaca gagtcctgct 3181 caatgatgga ggctattatg atccagagac aggcgtgttc acagcgccac tggctggacg 3241 ctacttgctg agcgcggtgc tgactgggca ccggcacgag aaagtggagg ccgtgctgtc 3301 ccgctccaac cagggcgtgg cccgcgtaga ctccggtggc tacgagcctg agggcctgga 3361 gaataagccg gtggccgaga gccagcccag cccgggcacc ctgggcgtct tcagcctcat 3421 cctgccgctg caggccgggg acacggtctg cgtcgacctg gtcatggggc agctggcgca 3481 ctcggaggag ccgctcacca tcttcagcgg ggccctgctc tatggggacc cagagcttga 3541 acacgcgtag actggggtcc cgcccgacgt gtctacgtcg gctgaagaga cagcgggggc 3601 ggcgggctcc tggggtctcg cctgagacgg ggcacctagc cctgggcgag cgccgcaccc 3661 gggcccgcag cggcaccgcg cccagagcgg cctctcccca cgcccggggc gcgccggctc 3721 agggaggctc ggggccgccc atgcagactt ttggcctggc gcgatccccc aagaacccct 3781 ccagggccgg cctgcggagg agccgatcct cgcaccctcc gctccctcca ctggccctcc 3841 aggtcgattc cctgggctcc aggctccccc gcgcgggcgc cgcccaccgc catactaaac 3901 gatcgaggaa taaagacact tggtttttct aaaaaaaaaa aaaaaaaaaa aaaaaaaaa

An exemplary human TNN amino acid sequence is set forth below (SEQ ID NO: 81; GenBank Accession No: AAI36620.1, Version 1, incorporated herein by reference):

   1 mslqemfrfp mglllgsvll vasapatlep pgcsnkeqqv tvshtykidv pksalvqvda   61 dpqplsddga sllalgeare eqniifrhni rlqtpqkdce lagsvqdlla rvkkleeemv  121 emkeqcsaqr ccqgvtdlsr hcsghgtfsl etcschceeg regpacerla cpgacsghgr  181 cvdgrclche pyvgadcgyp acpencsghg ecvrgvcqch edfmsedcse krcpgdcsgh  241 gfcdtgecyc eegftgldca qvvtpqglql lkntedsllv swepssqvdh yllsyyplgk  301 elsgkqiqvp keqhsyeilg llpgtkyivt lrnvknevss spqhllattd lavlgtawvt  361 detensldve wenpstevdy yklrygpmtg qevaevtvpk ssdpksrydi tglhpgteyk  421 itvvpmrgel egkpillngr teidsptnvv tdrvtedtat vswdpvqavi dkyvvrytsa  481 dgdtkemavh kdesstvltg lkpgeaykvy vwaergnqgs kkadtnalte idspanlvtd  541 rvtentatis wdpvqatidk yvvrytsadd qetrevlvgk eqsstvltgl rpgveytvhv  601 waqkgdresk kadtnaptdi dspknlvtdr vtenmatvsw dpvqaaidky vvrytsagge  661 trevpvgkeq sstvltglrp gmeymvhvwa qkgdqeskka dtkaqtdids pqnlvtdrvt  721 enmatvswdp vratidryvv rytsakdget revpvgkeqs stvltglrpg veytvhvwaq  781 kgaqeskkad tkaqtdidsp qnlvtdwvte ntatvswdpv qatidryvvh ytsangetre  841 vpvgkeqsst vltglrpgme ytvhvwaqkg nqeskkadtk aqteidgpkn lvtdwvtenm  901 atvswdpvqa tidkymvryt sadgetrevp vgkehsstvl tglrpgmeym vhvwaqkgaq  961 eskkadtkaq teldpprnlr psavtqsggi ltwtppsaqi hgyiltyqfp dgtvkemqlg 1021 redqrfalqg leqgatypvs lvafkggrrs rnvsttlstv garfphpsdc sqvqqnsnaa 1081 sglytiylhg dasrplqvyc dmetdgggwi vfqrrntgql dffkrwrsyv egfgdpmkef 1141 wlgldklhnl ttgtparyev rvdlqtanes ayaiydffqv asskeryklt vgkyrgtagd 1201 altyhngwkf ttfdrdndia lsncalthhg gwwyknchla npngrygetk hsegvnwepw 1261 kghefsipyv elkirphgys repvlgrkkr tlrgrlrtf

An exemplary human TNN nucleic acid sequence is set forth below (SEQ ID NO: 82; GenBank Accession No: NM_022093.1, Version 1, incorporated herein by reference):

   1 aagtaccaag gtctgcggca ggaggagacc ggctcacagg agcagcagca ttggaagagg   61 cacccagcag cctcccaggc atcctggagg gtctgctccc tgtctttcca aggatgagtc  121 tccaggagat gttccgcttc cctatggggc tcctgcttgg ctctgtgctc ctggtggctt  181 cggccccagc cactctggag cctcccggct gcagcaacaa ggagcaacag gtcactgtca  241 gccacaccta caagatcgat gtgcccaagt ctgccttggt tcaggttgac gctgaccctc  301 agcccctcag tgacgatggg gcttcgctct tggccctggg ggaggccagg gaggaacaga  361 acatcatctt caggcacaac atccgccttc agacgccaca gaaggactgc gagttggcag  421 gcagtgtcca ggacctcctg gcccgggtga agaagctgga ggaagagatg gtggagatga  481 aggaacagtg tagtgcccag cgctgctgcc agggagtcac tgatctaagc cgccactgca  541 gcggccacgg gaccttctcc ctggagacct gcagctgcca ctgcgaagag ggcagggagg  601 gccccgcctg cgagcggctg gcctgccccg gggcgtgcag cggccacggg cgttgcgtgg  661 acgggcgctg cctgtgccat gagccctacg tgggtgccga ctgcggctac ccggcctgcc  721 ctgagaactg cagcggacac ggcgagtgcg tgcgcggcgt gtgccagtgc cacgaagact  781 tcatgtcgga ggactgcagc gagaagcgct gtcccggcga ctgcagcggc cacggcttct  841 gtgacacggg cgagtgctac tgcgaggagg gcttcacagg cctggactgt gcccaggtgg  901 tcaccccaca gggcctgcag ctgctcaaga acacggagga ttctctgctg gtgagctggg  961 agccctccag ccaggtggat cactacctcc tcagctacta ccccctgggg aaggagctct 1021 ctgggaagca gatccaagtg cccaaggagc agcacagcta tgagattctt ggtttgctgc 1081 ctggaaccaa gtacatagtc accctgcgta acgtcaagaa tgaagtttct agcagcccac 1141 agcatctact tgccaccaca gaccttgctg tgcttggcac tgcctgggtg acagatgaga 1201 ctgagaactc ccttgacgtg gagtgggaaa acccctcaac tgaggtggac tactacaagc 1261 tgcgatatgg ccccatgaca ggacaggagg tagctgaggt cactgtgccc aagagcagtg 1321 accccaagag ccgatatgac atcactggtc tgcacccggg gactgagtat aagatcacgg 1381 tggtgcccat gagaggagag ctggagggca agccgatcct cctgaatggc aggacagaaa 1441 ttgacagtcc aaccaatgtt gtcactgatc gagtgactga agacacagca actgtctcct 1501 gggacccagt gcaggctgtc atagacaagt atgtagtgcg ctacacttct gctgatgggg 1561 acaccaagga aatggcagtg cacaaggatg agagcagcac tgtcctgacg ggcctgaagc 1621 caggagaggc atacaaggtc tacgtgtggg ctgaaagggg caaccagggg agcaagaaag 1681 ctgacaccaa tgccctcaca gaaattgaca gcccagcaaa cctggtgact gaccgggtga 1741 ctgagaatac cgccaccatc tcctgggacc cggtacaggc caccattgac aagtacgtgg 1801 tgcgctacac ctctgctgac gaccaagaga ccagagaggt tctggtgggg aaggagcaga 1861 gcagcactgt cctgacaggc ctgaggccag gtgtggagta cacagtgcat gtctgggccc 1921 agaaggggga ccgagagagc aagaaggctg acaccaacgc cccgacagat attgacagcc 1981 ccaaaaacct ggtgactgac cgggtgacag agaatatggc cacggtctcc tgggacccgg 2041 tgcaggccgc cattgacaag tacgtggtgc gctacacctc tgctggtgga gagaccaggg 2101 aggttccggt ggggaaggag cagagcagca cagtcctgac aggcctgaga ccgggtatgg 2161 agtacatggt gcacgtgtgg gcccagaagg gggaccagga gagcaagaag gccgacacca 2221 aggcccagac agacattgac agcccccaaa acctggtgac cgaccgggtg acagagaata 2281 tggccactgt ctcctgggac ccggtgcggg ccaccattga caggtatgtg gtgcgctaca 2341 cctctgccaa ggacggagag accagggagg ttccggtggg gaaggagcag agtagcactg 2401 tcctgacggg cctgaggccg ggtgtggagt acacggtgca cgtgtgggcc cagaaggggg 2461 cccaggagag caagaaggct gacaccaagg cccagacaga cattgacagc ccccaaaacc 2521 tggtcactga ctgggtgaca gagaatacag ccactgtctc ctgggacccg gtgcaggcca 2581 ccattgacag gtatgtggtg cactacacgt ctgccaacgg agagaccagg gaggttccag 2641 tggggaagga gcagagcagc actgtcctga cgggcctgag gccgggcatg gagtacacgg 2701 tgcacgtgtg ggcccagaag gggaaccagg agagcaagaa ggctgacacc aaggcccaga 2761 cagaaattga cggccccaaa aacctagtga ctgactgggt gacggagaat atggccactg 2821 tctcctggga cccggttcag gccaccattg acaagtacat ggtgcgctac acctctgctg 2881 acggagagac cagggaggtt ccggtgggga aggagcacag cagcactgtc ctgacgggcc 2941 tgagaccagg catggagtac atggtgcacg tgtgggccca gaagggggcc caggagagca 3001 agaaggctga caccaaggcc cagacagaac tcgaccctcc cagaaacctt cgtccatctg 3061 ctgtaacgca gtctggtggc atattgacct ggacgccccc ctctgctcag atccacggct 3121 acattctgac ttaccagttc ccagatggca cagttaagga gatgcagctg ggacgggaag 3181 accagaggtt tgcgttgcaa ggccttgagc aaggcgccac ctaccctgtc tcccttgttg 3241 cctttaaggg tggtcgccgg agcagaaatg tatccaccac cctctccaca gttggtgccc 3301 gtttcccaca cccttcggac tgcagtcagg ttcagcagaa cagcaatgcc gccagtggtc 3361 tgtacaccat ctacctgcat ggcgatgcca gccggcccct gcaggtgtac tgtgacatgg 3421 aaacggacgg aggtggctgg attgtcttcc agaggcggaa cactgggcag ctggatttct 3481 tcaagcgatg gaggagctat gtggaaggct ttggggaccc catgaaggag ttctggcttg 3541 gacttgacaa gctacacaac ctcaccaccg gcactccagc gcggtatgag gtgagagtgg 3601 atttacagac tgccaatgaa tctgcctatg ctatatatga tttcttccaa gtggcctcca 3661 gcaaggagcg gtataagctg acagttggga aatacagagg cacggcaggg gatgctctta 3721 cttaccacaa tggatggaag tttacaactt ttgacagaga caatgatatc gcactcagca 3781 actgtgccct gacacatcat ggtggctggt ggtataagaa ctgccacttg gccaacccta 3841 atggcagata tggggagacc aagcacagtg agggggtgaa ctgggagcct tggaaaggac 3901 atgaattctc cattccttac gtggagttga aaatccgccc tcatggctac agcagggagc 3961 ctgtcctggg cagaaagaag cggacgctga gaggaaggct gcgaacgttc tgatggcccg 4021 tgtgagcagt cctcgcagga gacaccacca gctgtggcag cttggggcgg ggtgggtagt 4081 ggtcactgcg gtctgggagt gctcagatag cccgcagaac aaatcatgtc accaagcttc 4141 aagccatgga ggttccttcc ctctcacctg catttttgcc cgtctttatg agggtcttga 4201 aaatcaaaat agtagttgca cagtatgtgt aggaaagaca gtactggaac ggcaaggttt 4261 ctcagcttat cttcagcaac atatatactg gattagggca agagaaggaa tcacccagca 4321 cttcaccagt tggaaatctc tggaaattta catctatgta tttaaagttc tgctaatgca 4381 aatcttttct ctggaaagaa gcacagagga ggagttctga tgacccaggg gttagggctg 4441 agacaaccgg acgtttgtca cctcctttcc cattgggttt ttaggaaaac agtgtgaacc 4501 tccccctttt aatttctggt gttatgagga agaataaagg ggataaaagg ggctaagatg 4561 gactcatgtt tagctaagtt ctgacttgta tccagcatgc tggagaccaa agctgccgcc 4621 ttactgctat ttttaagtgc cctcttttca gtcatttgca taattgcgtc catagagctg 4681 catatgttgt gaataaattc tcactcattt caactttgaa taatttgact gtcttgataa 4741 ttggttcctc ccaaagactc ttctgcaact cccattcatg cccaccaggc ctcagactcc 4801 ctcttttccc cgccctgcac tattggagcc ctgggttttg tgggagtgct cagcaccgtg 4861 agtcttactg tttgatcgga cagttagcaa gatcagatcc tttttgctta ttttctatca 4921 ctttggaggg ttttctgtag caaaatcagt gaccaatgaa gtaacttaaa ttcctattga 4981 agaaaaaaaa taataaacca cttgattt

An exemplary human miR-211 nucleic acid sequence is set forth below (SEQ ID NO: 83; GenBank Accession No: NR_029624.1, Version 1, incorporated herein by reference):

 1 tcacctggcc atgtgacttg tgggcttccc tttgtcatcc ttcgcctagg gctctgagca 61 gggcagggac agcaaagggg tgctcagttg tcacttccca cagcacggag

An exemplary human CD5L amino acid sequence is set forth below (SEQ ID NO: 84; GenBank Accession No: AAQ88858.1, Version 1, incorporated herein by reference):

  1 mallfslila ictrpgflas psgvrlvggl hrcegrveve qkgqwgtvcd dgwdikdvav  61 lcrelgcgaa sgtpsgilye ppaekeqkvl iqsvsctgte dtlaqceqee vydcshdeda 121 gascenpess fspvpegvrl adgpghckgr vevkhqnqwy tvcqtgwslr aakvvcrqlg 181 cgravltqkr cnkhaygrkp iwlsqmscsg reatlqdcps gpwgkntcnh dedtwveced 241 pfdlrlvggd nlcsgrlevl hkgvwgsvcd dnwgekedqv vckqlgcgks lspsfrdrkc 301 ygpgvgriwl dnvrcsgeeq sleqcqhrfw gfhdcthqed vavicsv

An exemplary human CD5L nucleic acid sequence is set forth below (SEQ ID NO: 85; GenBank Accession No: NM_005894.2, Version 2, incorporated herein by reference):

   1 gatcatctga taatgctttg cctgcactca ggacctgtct ttgtccctcc tcttaacata   61 cttgcagcta aaactaaata ttgctgcttg gggacctcct tctagcctta aatttcagct  121 catcaccttc acctgccttg gtcatggctc tgctattctc cttgatcctt gccatttgca  181 ccagacctgg attcctagcg tctccatctg gagtgcggct ggtggggggc ctccaccgct  241 gtgaagggcg ggtggaggtg gaacagaaag gccagtgggg caccgtgtgt gatgacggct  301 gggacattaa ggacgtggct gtgttgtgcc gggagctggg ctgtggagct gccagcggaa  361 cccctagtgg tattttgtat gagccaccag cagaaaaaga gcaaaaggtc ctcatccaat  421 cagtcagttg cacaggaaca gaagatacat tggctcagtg tgagcaagaa gaagtttatg  481 attgttcaca tgatgaagat gctggggcat cgtgtgagaa cccagagagc tctttctccc  541 cagtcccaga gggtgtcagg ctggctgacg gccctgggca ttgcaaggga cgcgtggaag  601 tgaagcacca gaaccagtgg tataccgtgt gccagacagg ctggagcctc cgggccgcaa  661 aggtggtgtg ccggcagctg ggatgtggga gggctgtact gactcaaaaa cgctgcaaca  721 agcatgccta tggccgaaaa cccatctggc tgagccagat gtcatgctca ggacgagaag  781 caacccttca ggattgccct tctgggcctt gggggaagaa cacctgcaac catgatgaag  841 acacgtgggt cgaatgtgaa gatccctttg acttgagact agtaggagga gacaacctct  901 gctctgggcg actggaggtg ctgcacaagg gcgtatgggg ctctgtctgt gatgacaact  961 ggggagaaaa ggaggaccag gtggtatgca agcaactggg ctgtgggaag tccctctctc 1021 cctccttcag agaccggaaa tgctatggcc ctggggttgg ccgcatctgg ctggataatg 1081 ttcgttgctc aggggaggag cagtccctgg agcagtgcca gcacagattt tgggggtttc 1141 acgactgcac ccaccaggaa gatgtggctg tcatctgctc aggatagtat cctggtgttg 1201 cttgacctgg cccccctggc cccgcctgcc ctctgcttgt tctcctgagc cctgattatc 1261 ctcatactca ttctggggct caggcttgag ccactactcc ctcatcccct caggagtctg 1321 aacactgggc ttatgcctta ctctcaggga caagcagccc ccattgctgc ctgtagatgt 1381 gagctgttga gttccctctt gctggggaag atgagcttcc atgtatcctg tgctcaaccc 1441 tgaccctttg acactggttc tggcctttcc tgccttttct caagctgcct ggaatcctca 1501 aacctgtcac tttggtcaga tgtgcagacc attactaagg tctatgtctg caaacattac 1561 taatctaggt cctattacta atctatgtct gcaaacatta aaggaatgaa acaatgaaag 1621 gaacatttga aagaaaatgt gggtagacaa tttcttgcaa cttgggggaa agtttagaat 1681 tcttttgatt ggactacttt tttttttttt cctcaagctt caggtgacca caatagcaac 1741 acctccctat tctgttattt cttagtgtag gtagacaatt ctttcaggag cagagcagcg 1801 tcctataatc ctagaccttt tcatgacgtg taaaaaatga tgtttcatcc tctgattgcc 1861 ccaataaaaa tctttgttgt ccatccctat acaacctgcc aacatggttg acatttaatg 1921 agaggaatgt caaaaataca ttttacttta ttcaaagaaa aatatattgg ttactgggaa 1981 aaggtcaaga aagaggcaga aagagatcag ggagggctaa agttgtgtct tatgccaagc 2041 gaaagtgaaa aatatcattt tcactttatc aactgagact ttggggcctg taagcttgag 2101 gcaagacaga aataagagaa tcaagacttg attgtaaaaa ttgacaactt tagattctga 2161 ggctaggctg agtacttatt atacggctac atttacacat ttacacttat ctaataaatc 2221 agatttcaca gtctcaaaaa aaaaaaaa

An exemplary human IL12RB2 amino acid sequence is set forth below (SEQ ID NO: 86; GenBank Accession No: AAI43250.1, Version 1, incorporated herein by reference):

  1 mahtfrgcsl afmfiitwll ikakidackr gdvtvkpshv illgstvnit cslkprqgcf  61 hysrrnklil ykfdrrinfh hghslnsqvt glplgttlfv cklacinsde iqicgaeifv 121 gvapeqpqnl sciqkgeqgt vactwergrd thlyteytlq lsgpknltwq kqckdiycdy 181 ldfginltpe spesnftakv tavnslgsss slpstftfld ivrplppwdi rikfqkasvs 241 rctlywrdeg lvllnrlryr psnsrlwnmv nvtkakgrhd lldlkpftey efqissklhl 301 ykgswsdwse slraqtpeee ptgmldvwym krhidysrqq islfwknlsv seargkilhy 361 qvtlqeltgg kamtqnitgh tswttviprt gnwavavsaa nskgsslptr inimnlceag 421 llaprhvsan segmdnilvt wqpprkdpsa vqeyvvewre lhpggdtqvp lnwlrsrpyn 481 vsaliseipy rvsqnshpin slqprvtyvl wmtaltaage sshgnerefc lqgkanwmaf 541 vapsiciaii mvgifsthyf qqkvfvllaa lrpqwcsrei pdpanstcak kypiaeektq 601 lpldrllidw ptpedpeplv isevlhqvtp vfrhppcsnw pgrekgiggh qasekdmmhs 661 assppppral qaesrqlvdl ykvlesrgsd pkpenpacpw tvlpagdlpt hdgylpsnid 721 dlpsheapla dsleelepqh islsvfpsss lhpltfscgd kltldqlkmr cdslml

An exemplary human IL12RB2 nucleic acid sequence is set forth below (SEQ ID NO: 87; GenBank Accession No: NM_001559.2, Version 2, incorporated herein by reference):

   1 tgcagagcac agagaaagga catctgcgag gaaagttccc tgatggctgt caacaaagtg   61 ccacgtctct atggctgtga acgctgagca cacgatttta tcgcgcctat catatcttgg  121 tgcataaacg cacctcacct cggtcaaccc ttgctccgtc ttatgagaca ggctttatta  181 tccgcatttt atatgagggg aaactgacgg tggagagaga attatcttgc tcaaggcgac  241 acagcagagc ccacaggtgg cagaatccca cccgagcccg cttcgacccg cggggtggaa  301 accacgggcg cccgcccggc tgcgcttcca gagctgaact gagaagcgag tcctctccgc  361 cctgcggcca ccgcccagcc ccgacccccg ccccggcccg atcctcactc gccgccagct  421 ccccgcgccc accccggagt tggtggcgca gaggcgggag gcggaggcgg gagggcgggc  481 gctggcaccg ggaacgcccg agcgccggca gagagcgcgg agagcgcgac acgtgcggcc  541 cagagcaccg gggccacccg gtccccgcag gcccgggacc gcgcccgctg gcaggcgaca  601 cgtggaagaa tacggagttc tataccagag ttgattgttg atggcacata cttttagagg  661 atgctcattg gcatttatgt ttataatcac gtggctgttg attaaagcaa aaatagatgc  721 gtgcaagaga ggcgatgtga ctgtgaagcc ttcccatgta attttacttg gatccactgt  781 caatattaca tgctctttga agcccagaca aggctgcttt cactattcca gacgtaacaa  841 gttaatcctg tacaagtttg acagaagaat caattttcac catggccact ccctcaattc  901 tcaagtcaca ggtcttcccc ttggtacaac cttgtttgtc tgcaaactgg cctgtatcaa  961 tagtgatgaa attcaaatat gtggagcaga gatcttcgtt ggtgttgctc cagaacagcc 1021 tcaaaattta tcctgcatac agaagggaga acaggggact gtggcctgca cctgggaaag 1081 aggacgagac acccacttat acactgagta tactctacag ctaagtggac caaaaaattt 1141 aacctggcag aagcaatgta aagacattta ttgtgactat ttggactttg gaatcaacct 1201 cacccctgaa tcacctgaat ccaatttcac agccaaggtt actgctgtca atagtcttgg 1261 aagctcctct tcacttccat ccacattcac attcttggac atagtgaggc ctcttcctcc 1321 gtgggacatt agaatcaaat ttcaaaaggc ttctgtgagc agatgtaccc tttattggag 1381 agatgaggga ctggtactgc ttaatcgact cagatatcgg cccagtaaca gcaggctctg 1441 gaatatggtt aatgttacaa aggccaaagg aagacatgat ttgctggatc tgaaaccatt 1501 tacagaatat gaatttcaga tttcctctaa gctacatctt tataagggaa gttggagtga 1561 ttggagtgaa tcattgagag cacaaacacc agaagaagag cctactggga tgttagatgt 1621 ctggtacatg aaacggcaca ttgactacag tagacaacag atttctcttt tctggaagaa 1681 tctgagtgtc tcagaggcaa gaggaaaaat tctccactat caggtgacct tgcaggagct 1741 gacaggaggg aaagccatga cacagaacat cacaggacac acctcctgga ccacagtcat 1801 tcctagaacc ggaaattggg ctgtggctgt gtctgcagca aattcaaaag gcagttctct 1861 gcccactcgt attaacataa tgaacctgtg tgaggcaggg ttgctggctc ctcgccaggt 1921 ctctgcaaac tcagagggca tggacaacat tctggtgact tggcagcctc ccaggaaaga 1981 tccctctgct gttcaggagt acgtggtgga atggagagag ctccatccag ggggtgacac 2041 acaggtccct ctaaactggc tacggagtcg accctacaat gtgtctgctc tgatttcaga 2101 gaacataaaa tcctacatct gttatgaaat ccgtgtgtat gcactctcag gggatcaagg 2161 aggatgcagc tccatcctgg gtaactctaa gcacaaagca ccactgagtg gcccccacat 2221 taatgccatc acagaggaaa aggggagcat tttaatttca tggaacagca ttccagtcca 2281 ggagcaaatg ggctgcctcc tccattatag gatatactgg aaggaacggg actccaactc 2341 ccagcctcag ctctgtgaaa ttccctacag agtctcccaa aattcacatc caataaacag 2401 cctgcagccc cgagtgacat atgtcctgtg gatgacagct ctgacagctg ctggtgaaag 2461 ttcccacgga aatgagaggg aattttgtct gcaaggtaaa gccaattgga tggcgtttgt 2521 ggcaccaagc atttgcattg ctatcatcat ggtgggcatt ttctcaacgc attacttcca 2581 gcaaaaggtg tttgttctcc tagcagccct cagacctcag tggtgtagca gagaaattcc 2641 agatccagca aatagcactt gcgctaagaa atatcccatt gcagaggaga agacacagct 2701 gcccttggac aggctcctga tagactggcc cacgcctgaa gatcctgaac cgctggtcat 2761 cagtgaagtc cttcatcaag tgaccccagt tttcagacat cccccctgct ccaactggcc 2821 acaaagggaa aaaggaatcc aaggtcatca ggcctctgag aaagacatga tgcacagtgc 2881 ctcaagccca ccacctccaa gagctctcca agctgagagc agacaactgg tggatctgta 2941 caaggtgctg gagagcaggg gctccgaccc aaagcccgaa aacccagcct gtccctggac 3001 ggtgctccca gcaggtgacc ttcccaccca tgatggctac ttaccctcca acatagatga 3061 cctcccctca catgaggcac ctctcgctga ctctctggaa gaactggagc ctcagcacat 3121 ctccctttct gttttcccct caagttctct tcacccactc accttctcct gtggtgataa 3181 gctgactctg gatcagttaa agatgaggtg tgactccctc atgctctgag tggtgaggct 3241 tcaagcctta aagtcagtgt gccctcaacc agcacagcct gccccaattc ccccagcccc 3301 tgctccagca gctgtcatct ctgggtgcca ccatcggtct ggctgcagct agaggacagg 3361 caagccagct ctgggggagt cttaggaact gggagttggt cttcactcag atgcctcatc 3421 ttgcctttcc cagggcctta aaattacatc cttcactgtg tggacctaga gactccaact 3481 tgaattccta gtaactttct tggtatgctg gccagaaagg gaaatgagga ggagagtaga 3541 aaccacagct cttagtagta atggcataca gtctagagga ccattcatgc aatgactatt 3601 tctaaagcac ctgctacaca gcaggctgta cacagcagat cagtactgtt caacagaact 3661 tcctgagatg atggaaatgt tctacctctg cactcactgt ccagtacatt agacactagg 3721 cacattggct gttaatcact tggaatgtgt ttagcttgac tgaggaatta aattttgatt 3781 gtaaatttaa atcgccacac atggctagtg gctactgtat tggagtgcac agctctagat 3841 ggctcctaga ttattgagag ccttcaaaac aaatcaacct agttctatag atgaagacat 3901 aaaagacact ggtaaacacc aaggtaaaag ggcccccaag gtggtcatga ctggtctcat 3961 ttgcagaagt ctaagaatgt acctttttct ggccgggcgt ggtagctcat gcctgtaatc 4021 ccagcacttt gggaggctga

An exemplary human FAIM3 amino acid sequence is set forth below (SEQ ID NO: 88; GenBank Accession No: EAW93517.1, Version 1, incorporated herein by reference):

  1 mdfwlwplyf lpvsgalril pevkvegelg gsvtikcplp emhvriylcr emagsgtcgt  61 vvsttnfika eykgrvtlkq yprknlflve vtqltesdsg vyacgagmnt drgktqkvtl 121 nvhseyepsw eeqpmpetpk wfhlpylfqm payassskfv trvttpaqrg kvppvhhssp 181 ttqithrprv srassvagdk prtflpstta skisalegll kpqtpsynhh trlhrqrald 241 ygsqsgregq gfhiliptil glfllallgl vvkraverrk alsrrarrla vrmralessq 301 rprgsprprs qnniysacpr rargadaagt geapvpgpga plppaplqvs espwlhapsl 361 ktsceyvsly hqpaammeds dsddyinvpa

An exemplary human FAIM3 nucleic acid sequence is set forth below (SEQ ID NO: 89; GenBank Accession No: NM_005449.4, Version 4, incorporated herein by reference):

   1 agcctgagaa tagttagcaa acaagggagg ttgtcatttc ctcatcgtca agctttgttc   61 ctcgtggggg ctagaaatct ctttccagtt ccagattgtg aagggttcct gagtaagcag  121 cgtgtctcca tccccctctc taggggctct tggatggacc ttgcactcta gaagggacaa  181 tggacttctg gctttggcca ctttacttcc tgccagtatc gggggccctg aggatcctcc  241 cagaagtaaa ggtagagggg gagctgggcg gatcagttac catcaagtgc ccacttcctg  301 aaatgcatgt gaggatatat ctgtgccggg agatggctgg atctggaaca tgtggtaccg  361 tggtatccac caccaacttc atcaaggcag aatacaaggg ccgagttact ctgaagcaat  421 acccacgcaa gaatctgttc ctagtggagg taacacagct gacagaaagt gacagcggag  481 tctatgcctg cggagcgggc atgaacacag accggggaaa gacccagaaa gtcaccctga  541 atgtccacag tgaatacgag ccatcatggg aagagcagcc aatgcctgag actccaaaat  601 ggtttcatct gccctatttg ttccagatgc ctgcatatgc cagttcttcc aaattcgtaa  661 ccagagttac cacaccagct caaaggggca aggtccctcc agttcaccac tcctccccca  721 ccacccaaat cacccaccgc cctcgagtgt ccagagcatc ttcagtagca ggtgacaagc  781 cccgaacctt cctgccatcc actacagcct caaaaatctc agctctggag gggctgctca  841 agccccagac gcccagctac aaccaccaca ccaggctgca caggcagaga gcactggact  901 atggctcaca gtctgggagg gaaggccaag gatttcacat cctgatcccg accatcctgg  961 gccttttcct gctggcactt ctggggctgg tggtgaaaag ggccgttgaa aggaggaaag 1021 ccctctccag gcgggcccgc cgactggccg tgaggatgcg cgccctggag agctcccaga 1081 ggccccgcgg gtcgccgcga ccgcgctccc aaaacaacat ctacagcgcc tgcccgcggc 1141 gcgctcgtgg agcggacgct gcaggcacag gggaggcccc cgttcccggc cccggagcgc 1201 cgttgccccc cgccccgctg caggtgtctg aatctccctg gctccatgcc ccatctctga 1261 agaccagctg tgaatacgtg agcctctacc accagcctgc cgccatgatg gaggacagtg 1321 attcagatga ctacatcaat gttcctgcct gacaactccc cagctatccc ccaaccccag 1381 gctcggactg tggtgccaag gagtctcatc tatctgctga tgtccaatac ctgcttcatg 1441 tgttctcaga gccctcatca cttcccatgc cccatctcga ctcccatccc catctatctg 1501 tgccctgagc atggctctgc ccccaggtcg tcttgcacac cttggcagcc ccctgtagtt 1561 gacaggtaag ctgtaggcat gtagagcaat tgtcccaatg ccacttgctt cctttccaag 1621 ccgtcgaaca gactgtggga tttgcagagt gtttcttcca tgtctttgac cacagggttg 1681 ttgctgccca ggctctagat cacatggcat caggctgggg cagaggcata gctattgtct 1741 cgggcatcct tcccagggtt gggtcttaca caaatagaag gctcttgctc tgagttatgt 1801 gacatgcctc agccccatgg actaagcagg ggtctggtat aaaaacactc ctggaaacgc 1861 ctttgccctg atccaaatgt tagcacttgc tagtgaacgt ctacttatct caagttctat 1921 gctaaaggca atttatcttg atgtgatgat aaaccaaact tattagcaag atatgcatat 1981 atatccataa attctcttta ctctgtctcc atcacttgat gcacataagt gccctgacct 2041 cagcatctcc cctctaaaaa aaaaaaaaaa aaagtatctc tttatctttc ttccatagcc 2101 tgacactgat atttgtgcac ttaccttaac tttggtctat tttattcatc caaaaccatt 2161 acatttcttg gttttcacaa atgttcccca tttcttagcc agttccagac aatgtatagc 2221 aagcagggga aggaaagcag tcaggagttc ctgggtggcc acggctctgc aatagcactt 2281 atgtcatgga agtgatatcc cacctcctac atatactctt tgcctaggtt tttggaacaa 2341 ggttatagtc agacactgta tctttagatt gatgtcgacc acaaagttca gccagagctt 2401 gaggctagat gcacagcctt gctattggga agaaggcctt ttctagctgt acaacacagt 2461 ctcactgggc attcatccag aaatagagaa gaaagtctgc cagacttgag ttatgttgtc 2521 ttttattagc agggaatgtc atcacagatt ggatagtaca tccaggtgca atgtcaccat 2581 cagcaaggtc agcttgacac tcaagtggaa gattagggaa gaatgactag gataaaaaaa 2641 aaaggagggc accaagggaa agggatgatg gggtgagctg gcgagtgtgg gtgggaaatg 2701 aaatgtttat tgaggatctg ctttgtgctg ggcactttaa tccacatttt atcgtttact 2761 tttcaaacag atgcacctta cccccacccc aatgctctgt ccctgcagat atcagaagac 2821 agtgtgattt tcatgctctg aagttcagtt ttacatccaa gcatccctct ctgtttttta 2881 acaatccaaa gacaggccaa aaaaagcacc acagtttatt aagtacttac taagcaccca 2941 tccactgccc cacactgtgg caaggattgt gaggggtaaa gaagcatggg gcacaatatt 3001 ctgctgcctt catgtaactt acagtctcac aaataaatag aacttcagtt gaaatactga 3061 cattaattaa atagagttgt aataaaaaaa aaaaaaaaaa aaaaaaaaa

An exemplary human PTCRA amino acid sequence is set forth below (SEQ ID NO: 90; GenBank Accession No: AAI53830.1, Version 1, incorporated herein by reference):

  1 magtwlllll algcpalptg vggtpfpsla ppimllvdgk qqmvvvclvl dvappgldsp  61 iwfsagngsa ldaftygpsp atdgtwtnla hlslpseela sweplichtg pgaeghsrst 121 qpmhlsgeas tartcpqepl rgtpggalwl gvlrlllfkl llfdllltcs clcdpagplp 181 spatttrlra lgshrlhpat etggreatss prpqprdrrw gdtppgrkpg spvwgegsyl 241 ssyptcpaqa wcsrsalrap ssslgaffag dlppplqaga a

An exemplary human PTCRA nucleic acid sequence is set forth below (SEQ ID NO: 91; GenBank Accession No: NM_001243168.1, Version 1, incorporated herein by reference):

   1 tagaaggcag tcttgtgggt gcctcctccc ccagccgcaa ctcaggtctg cagctgggtc   61 ctgcctcctt ccgagtgggc catggccggt acatggctgc tacttctcct ggcccttggg  121 tgtccagccc tacccacagg tgtgggcggc acaccctttc cttctctggc cccaccaatc  181 atgctgctgg tggatggaaa gcagcagatg gtggtggtct gcctggtcct tgatgttgca  241 ccccctggcc ttgacagccc catctggttc tcagccggca atggcagtgc actggatgcc  301 ttcacctatg gcccttcccc agcaacggat ggcacctgga ccaacttggc ccatctctcc  361 ctgccttctg aggagctggc atcctgggag cctttggtct gccacactgg gcctggggct  421 gagggtcaca gcaggagtac acagcccatg catctgtcag gagaggcttc tacagccagg  481 acctgccccc aggagcctct cagggggggc tgcgggctcc tgcgggctcc tgagcggttc  541 ctcctcgcag ggacaccggg tggggcgctg tggctggggg tcctgcggct gctgctcttc  601 aagctgctgc tgtttgacct gctcctgacc tgcagctgcc tgtgcgaccc cgcgggcccg  661 ctgccttccc ccgcaaccac cacccgcctg cgagccctcg gctcccatcg actgcacccg  721 gccacggaga ctgggggacg agaggccacc agctcaccca gaccccagcc tcgggaccgc  781 cgctggggtg acacccctcc gggtcggaag cccgggagcc cagtatgggg ggaagggtct  841 tacctcagca gttaccccac ttgcccagca caggcctggt gctcaagatc tgccctcagg  901 gctccttcct ccagtcttgg agcatttttt gcaggtgacc tgcctcctcc tctgcaggct  961 ggagctgcct gagggcaggg ctctacctcc cctgcgtcac actgtgtgag gctgtgtctc 1021 tgccatccaa aagggggccc cttgagaatg gtgatccacc cagttacagg ggcatttagg 1081 gagcagatga ctgagaacat taaaaaagaa cttaaatgac acagcaaaaa aaaaaaaaaa 1141 aa

An exemplary human CD2 amino acid sequence is set forth below (SEQ ID NO: 92; GenBank Accession No: AAA51946.1, Version 1, incorporated herein by reference):

  1 msfpckfvas fllifnvssk gavskeitna letwgalgqd inldipsfqm sddiddikwe  61 ktsdkkkiaq frkeketfke kdtyklfkng tlkikhlktd dqdiykvsiy dtkgknvlek 121 ifdlkiqery skpkiswtci nttltcevmn gtdpelnlyq dgkhlklsqr vithkwttsl 181 sakfkctagn kvskessvep vscpekgldi yliigicggg sllmvfvall vfyitkrkkq 241 rsrrndeele trahrvatee rgrkphqipa stpqnpatsq hpppppghrs qapshrpppp 301 ghrvqhqpqk rppapsgtqv hqqkgpplpr prvqpkppmg qqkthcplpl ikkdrnclfq

An exemplary human CD2 nucleic acid sequence is set forth below (SEQ ID NO: 93; GenBank Accession No: NM_001328609.1, Version 1, incorporated herein by reference):

   1 agtctcactt cagttccttt tgcatgaaga gctcagaatc aaaagaggaa accaacccct   61 aagatgagct ttccatgtaa atttgtagcc agcttccttc tgattttcaa tgtttcttcc  121 aaaggtgcag tctccaaaga gattacgaat gccttggaaa cctggggtgc cttgggtcag  181 gacatcaact tggacattcc tagttttcaa atgagtgatg atattgacga tataaaatgg  241 gaaaaaactt cagacaagaa aaagattgca caattcagaa aagagaaaga gactttcaag  301 gaaaaagata catataagct atttaaaaat ggaactctga aaattaagca tctgaagacc  361 gatgatcagg atatctacaa ggtatcaata tatgatacaa aaggaaaaaa tgtgttggaa  421 aaaatatttg atttgaagat tcaagagagg gtctcaaaac caaagatctc ctggacttgt  481 atcaacacaa ccctgacctg tgaggtaatg aatggaactg accccgaatt aaacctgtat  541 caagatggga aacatctaaa actttctcag agggtcatca cacacaagtg gaccaccagc  601 ctgagtgcaa aattcaagtg cacagcaggg aacaaagtca gcaaggaatc cagtgtcgag  661 cctgtcagct gtccaggagg cagcatcctt ggccagagta atgggctctc tgcctggacc  721 cctcccagcc atcccacttc tcttcctttt gcagagaaag gtctggacat ctatctcatc  781 attggcatat gtggaggagg cagcctcttg atggtctttg tggcactgct cgttttctat  841 atcaccaaaa ggaaaaaaca gaggagtcgg agaaatgatg aggagctgga gacaagagcc  901 cacagagtag ctactgaaga aaggggccgg aagccccacc aaattccagc ttcaacccct  961 cagaatccag caacttccca acatcctcct ccaccacctg gtcatcgttc ccaggcacct 1021 agtcatcgtc ccccgcctcc tggacaccgt gttcagcacc agcctcagaa gaggcctcct 1081 gctccgtcgg gcacacaagt tcaccagcag aaaggcccgc ccctccccag acctcgagtt 1141 cagccaaaac ctccccatgg ggcagcagaa aactcattgt ccccttcctc taattaaaaa 1201 agatagaaac tgtctttttc aataaaaagc actgtggatt tctgccctcc tgatgtgcat 1261 atccgtactt ccatgaggtg ttttctgtgt gcagaacatt gtcacctcct gaggctgtgg 1321 gccacagcca cctctgcatc ttcgaactca gccatgtggt caacatctgg agtttttggt 1381 ctcctcagag agctccatca caccagtaag gagaagcaat ataagtgtga ttgcaagaat 1441 ggtagaggac cgagcacaga aatcttagag atttcttgtc ccctctcagg tcatgtgtag 1501 atgcgataaa tcaagtgatt ggtgtgcctg ggtctcacta caagcagcct atctgcttaa 1561 gagactctgg agtttcttat gtgccctggt ggacacttgc ccaccatcct gtgagtaaaa 1621 gtgaaataaa agctttgact agaaaaaaaa aaaaaaaaaa

An exemplary human CD6 amino acid sequence is set forth below (SEQ ID NO: 94; GenBank Accession No: AAH33755.1, Version 1, incorporated herein by reference):

  1 mwlffgitgl ltaalsghps pappdqlnts saeselwepg erlpvrltng ssscsgtvev  61 rleaswepac galwdsraae avcralgcgg aeaasqlapp tpelppppaa gntsvaanat 121 lagapallcs gaewrlcevv ehacrsdgrr arvtcaenra lrlvdgggac agrvemlehg 181 ewgsvcddtw dledahvvcr qlgcgwavqa lpglhftpgr gpihrdqvnc sgaeaylwdc 241 pglpgqhycg hkedagavcs ehqswrltgg adrcegqvev hfrgvwntvc dsewypseak 301 vlcqslgcgt averpkglph slsgrmyysc ngeeltlsnc swrfnnsnlc sqslaarvlc 361 sasrslhnls tpevpasvqt vtiessvtvk ienkesrelm llipsivlgi lllgslifia 421 fillrikgky alpvmvnhqh lpttipagsn syqpvpitip kevfmlpiqv qapppedsds 481 gsdsdyehyd fsaqppvalt tfynsqrhrv tdeevqqsrf qmppleegle elhashipta 541 npghcitdpp slgpqyhprs nsesstssge dycnspkskl ppwnpqvfss erssfleqpp 601 nlelagtqpa fsgppaddss stssgewyqn fqprllgwl

An exemplary human CD6 nucleic acid sequence is set forth below (SEQ ID NO: 95; GenBank Accession No: NM_006725.4, Version 4, incorporated herein by reference):

   1 gcagaccaaa accacaagca gaacaagcag gcgtgagaca ctcacaggtt gggtttgatc   61 gcatgcgtgt cggagaggag agagcagaga gagacacagg aacaagaaca gcaaagggta  121 gagcagacct gcgccagggg cgcacaacgg ccgtgtccac ctcccggccc caagatggtg  181 cttcccacag gcagccacgc gtagcagcca gagacagctc cagacatgtg gctcttcttc  241 gggatcactg gattgctgac ggcagccctc tcaggtcatc catctccagc cccacctgac  301 cagctcaaca ccagcagtgc agagagtgag ctctgggagc caggggagcg gcttccggtc  361 cgtctgacaa acgggagcag cagctgcagc gggacggtgg aggtgcggct cgaggcgtcc  421 tgggagcccg cgtgcggggc gctctgggac agccgcgccg ccgaggccgt gtgccgagca  481 ctgggctgcg gcggggcgga ggccgcctct cagctcgccc cgccgacccc tgagctgccg  541 cccccgcctg cagccgggaa caccagcgta gcagctaatg ccactctggc cggggcgccc  601 gccctcctgt gcagcggcgc cgagtggcgg ctctgcgagg tggtggagca cgcgtgccgc  661 agcgacggga ggcgggcccg tgtcacctgt gcagagaacc gcgcgctgcg cctggtggac  721 ggtggcggcg cctgcgccgg ccgcgtggag atgctggagc atggcgagtg gggatcagtg  781 tgcgatgaca cttgggacct ggaggacgcc cacgtggtgt gcaggcaact gggctgcggc  841 tgggcagtcc aggccctgcc cggcttgcac ttcacgcccg gccgcgggcc tatccaccgg  901 gaccaggtga actgctcggg ggccgaagct tacctgtggg actgcccggg gctgccagga  961 cagcactact gcggccacaa agaggacgcg ggcgcggtgt gctcagagca ccagtcctgg 1021 cgcctgacag ggggcgctga ccgctgcgag gggcaggtgg aggtacactt ccgaggggtc 1081 tggaacacag tgtgtgacag tgagtggtac ccatcggagg ccaaggtgct ctgccagtcc 1141 ttgggctgtg gaactgcggt tgagaggccc aaggggctgc cccactcctt gtccggcagg 1201 atgtactact catgcaatgg ggaggagctc accctctcca actgctcctg gcggttcaac 1261 aactccaacc tctgcagcca gtcgctggca gccagggtcc tctgctcagc ttcccggagt 1321 ttgcacaatc tgtccactcc cgaagtccct gcaagtgttc agacagtcac tatagaatct 1381 tctgtgacag tgaaaataga gaacaaggaa tctcgggagc taatgctcct catcccctcc 1441 atcgttctgg gaattctcct ccttggctcc ctcatcttca tagccttcat cctcttgaga 1501 attaaaggaa aatatgccct ccccgtaatg gtgaaccacc agcacctacc caccaccatc 1561 ccggcaggga gcaatagcta tcaaccggtc cccatcacca tccccaaaga agttttcatg 1621 ctgcccatcc aggtccaggc cccgccccct gaggactcag actctggctc ggactcagac 1681 tatgagcact atgacttcag cgcccagcct cctgtggccc tgaccacctt ctacaattcc 1741 cagcggcatc gggtcacaga tgaggaggtc cagcaaagca ggttccagat gccacccttg 1801 gaggaaggac ttgaagagtt gcatgcctcc cacatcccaa ctgccaaccc tggacactgc 1861 attacagacc cgccatccct gggccctcag tatcacccga ggagcaacag tgagtcgagc 1921 acctcttcag gggaggatta ctgcaatagt cccaaaagca agctgcctcc atggaacccc 1981 caggtgtttt cttcagagag gagttccttc ctggagcagc ccccaaactt ggagctggcc 2041 ggcacccagc cagccttttc agcagggccc ccggctgatg acagctccag cacctcatcc 2101 ggggagtggt accagaactt ccagccacca ccccagcccc cttcggagga gcagtttggc 2161 tgtccagggt cccccagccc tcagcctgac tccaccgaca acgatgacta cgatgacatc 2221 agcgcagcct aggccggggc cagccgaggc tcctggggtg gctctgaccc tctggcctcc 2281 tgctctacct actccctttc ccctttccca ccctcccagc tcacctcccc atggagctga 2341 gaggcctccc ttggagagat ggaaggaaac gttatacctt gtacccctcg gtctccatcc 2401 atcaagccaa acctgctgcc acagccctcc cccggcccca gatagcagcc ccagggagga 2461 tgctgcctcc aagaggtgtg agccctctgt ctcggggatg aacaagcaga gtctgggcta 2521 cctcttgaca gctggtggag gggagttggg gagctggact ggatgactct ggaggcccct 2581 tccaaacctc aagtgtccgg cgctttgatt gcctgagttt ctgacacttc agggcccaga 2641 ggtcctgcga ggggcagaac tggaccccca tgccagtgct gctgcaggag ggcccatata 2701 ctagggtctg ctgagctgtt gtcactgatc ggtgggcgct gggggggtag ggtagcacac 2761 cagctgtccc aggctttgct ccgggcggta actgcacttg ggcagggaat atagccttcc 2821 tgggcacaac tagctgacaa tgacaggttg actgtgtacc cccaaccaag gagctggggc 2881 ccaaggccag tcctgcccca gagacactcc aagtccgcca ggggcacaga ccagttctgc 2941 agtgactgtc cctggacaat gggtctttat tctgagtttc ctatggttta caaagagggc 3001 cccagcccag ccccaccaca gatcccagag ataggggccc agtctccatg ggggcaagga 3061 gcatagagat gttttccagg aaggggctca gaagctgcac taggccccga gtccccatgt 3121 gtctccttga attgatgagg atgctcctgg gagggatgcg tgactatgtg gtgttgcacc 3181 cggggctgca aacgtctccg tgcagccccc agagagaggc ccatgggctc agaccaggct 3241 ttgttgtcct gctctgagta tcctgagatt aaactgaatt gctgaatgaa aaaaaaaaaa 3301 aaaaaaaaa

An exemplary human CXCL13 amino acid sequence is set forth below (SEQ ID NO: 96; GenBank Accession No: AAH12589.1, Version 1, incorporated herein by reference):

 1 mkfistslll mllvsslspv qgvlevyyts lrcrcvqess vfiprrfidr iqilprgngc 61 prkeiivwkk nksivcvdpq aewiqrmmev lrkrssstlp vpvfkrkip

An exemplary human CXCL13 nucleic acid sequence is set forth below (SEQ ID NO: 97; GenBank Accession No: NM_006419.2, Version 2, incorporated herein by reference):

   1 gagaagatgt ttgaaaaaac tgactctgct aatgagcctg gactcagagc tcaagtctga   61 actctacctc cagacagaat gaagttcatc tcgacatctc tgcttctcat gctgctggtc  121 agcagcctct ctccagtcca aggtgttctg gaggtctatt acacaagctt gaggtgtaga  181 tgtgtccaag agagctcagt ctttatccct agacgcttca ttgatcgaat tcaaatcttg  241 ccccgtggga atggttgtcc aagaaaagaa atcatagtct ggaagaagaa caagtcaatt  301 gtgtgtgtgg accctcaagc tgaatggata caaagaatga tggaagtatt gagaaaaaga  361 agttcttcaa ctctaccagt tccagtgttt aagagaaaga ttccctgatg ctgatatttc  421 cactaagaac acctgcattc ttcccttatc cctgctctgg attttagttt tgtgcttagt  481 taaatctttt ccaggaaaaa gaacttcccc atacaaataa gcatgagact atgtaaaaat  541 aaccttgcag aagctgatgg ggcaaactca agcttcttca ctcacagcac cctatataca  601 cttggagttt gcattcttat tcatcaggga ggaaagtttc tttgaaaata gttattcagt  661 tataagtaat acaggattat tttgattata tacttgttgt ttaatgttta aaatttctta  721 gaaaacaatg gaatgagaat ttaagcctca aatttgaaca tgtggcttga attaagaaga  781 aaattatggc atatattaaa agcaggcttc tatgaaagac tcaaaaagct gcctgggagg  841 cagatggaac ttgagcctgt caagaggcaa aggaatccat gtagtagata tcctctgctt  901 aaaaactcac tacggaggag aattaagtcc tacttttaaa gaatttcttt ataaaattta  961 ctgtctaaga ttaatagcat tcgaagatcc ccagacttca tagaatactc agggaaagca 1021 tttaaagggt gatgtacaca tgtatccttt cacacatttg ccttgacaaa cttctttcac 1081 tcacatcttt ttcactgact ttttttgtgg ggggcggggc cggggggact ctggtatcta 1141 attctttaat gattcctata aatctaatga cattcaataa agttgagcaa acattttact 1201 taaaaaaaaa aaaaaaaaa

An exemplary human CD3D amino acid sequence is set forth below (SEQ ID NO: 98; GenBank Accession No: AEQ93556.1, Version 1, incorporated herein by reference):

 1 mehstflsgl vlatllsqvc qscveldpat vagiivtdvi atlllalgvf cfaghetgrl 61 sgaadtqall rndqvygplr drddagyshl ggnwarnk

An exemplary human CD3D nucleic acid sequence is set forth below (SEQ ID NO: 99; GenBank Accession No: BAJ000732.4, Version 4, incorporated herein by reference):

  1 agagaagcag acatcttcta gttcctcccc cactctcctc tttccggtac ctgtgagtca  61 gctaggggag ggcagctctc acccaggctg atagttcggt gacctggctt tatctactgg 121 atgagttccg ctgggagatg gaacatagca cgtttctctc tggcctggta ctggctaccc 181 ttctctcgca agtgagcccc ttcaagatac ctatagagga acttgaggac agagtgtttg 241 tgaattgcaa taccagcatc acatgggtag agggaacggt gggaacactg ctctcagaca 301 ttacaagact ggacctggga aaacgcatcc tggacccacg aggaatatat aggtgtaatg 361 ggacagatat atacaaggac aaagaatcta ccgtgcaagt tcattatcga atgtgccaga 421 gctgtgtgga gctggatcca gccaccgtgg ctggcatcat tgtcactgat gtcattgcca 481 ctctgctcct tgctttggga gtcttctgct ttgctggaca tgagactgga aggctgtctg 541 gggctgccga cacacaagct ctgttgagga atgaccaggt ctatcagccc ctccgagatc 601 gagatgatgc tcagtacagc caccttggag gaaactgggc tcggaacaag tgaacctgag 661 actggtggct tctagaagca gccattacca actgtacctt cccttcttgc tcagccaata 721 aatatatcct ctttcactca gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a

An exemplary human CD3E nucleic acid sequence is set forth below (SEQ ID NO: 101; GenBank Accession No: NM_16130.1, Version 1, incorporated herein by reference):

  1 mqsgthwrvl glcllsvgvw gqdewvvlrg itqtpykvsi sgttviltcp qypgseilwq  61 hndkniggde ddknigsded hlslkefsel eqsgyyvcyp rgskpedanf ylylrarvce 121 ncmemdvmsv ativivdici tggllllvyy wsknrkakak pvtrgagagg rqrgqnkerp 181 ppvpnpdyep irkgqrdlys glnqrri

An exemplary human CD3G amino acid sequence is set forth below (SEQ ID NO: 101; GenBank Accession No: NM_000733.3,Version 3, incorporated herein by reference):

   1 tattgtcaga gtcctcttgt ttggccttct aggaaggctg tgggacccag ctttcttcaa   61 ccagtccagg tggaggcctc tgccttgaac gtttccaagt gaggtaaaac ccgcaggccc  121 agaggcctct ctacttcctg tgtggggttc agaaaccctc ctcccctccc agcctcaggt  181 gcctgcttca gaaaatgaag tagtaagtct gctggcctcc gccatcttag taaagtaaca  241 gtcccatgaa acaaagatgc agtcgggcac tcactggaga gttctgggcc tctgcctctt  301 atcagttggc gtttgggggc aagatggtaa tgaagaaatg ggtggtatta cacagacacc  361 atataaagtc tccatctctg gaaccacagt aatattgaca tgccctcagt atcctggatc  421 tgaaatacta tggcaacaca atgataaaaa cataggcggt gatgaggatg ataaaaacat  481 aggcagtgat gaggatcacc tgtcactgaa ggaattttca gaattggagc aaagtggtta  541 ttatgtctgc taccccagag gaagcaaacc agaagatgcg aacttttatc tctacctgag  601 ggcaagagtg tgtgagaact gcatggagat ggatgtgatg tcggtggcca caattgtcat  661 agtggacatc tgcatcactg ggggcttgct gctgctggtt tactactgga gcaagaatag  721 aaaggccaag gccaagcctg tgacacgagg agcgggtgct ggcggcaggc aaaggggaca  781 aaacaaggag aggccaccac ctgttcccaa cccagactat gagcccatcc ggaaaggcca  841 gcgggacctg tattctggcc tgaatcagag acgcatctga ccctctggag aacactgcct  901 cccgctggcc caggtctcct ctccagtccc cctgcgactc cctgtttcct gggctagtct  961 tggaccccac gagagagaat cgttcctcag cctcatggtg aactcgcgcc ctccagcctg 1021 atcccccgct ccctcctccc tgccttctct gctggtaccc agtcctaaaa tattgctgct 1081 tcctcttcct ttgaagcatc atcagtagtc acaccctcac agctggcctg ccctcttgcc 1141 aggatattta tttgtgctat tcactccctt ccctttggat gtaacttctc cgttcagttc 1201 cctccttttc ttgcatgtaa gttgtccccc atcccaaagt attccatcta cttttctatc 1261 gccgtcccct tttgcagccc tctctgggga tggactgggt aaatgttgac agaggccctg 1321 ccccgttcac agatcctggc cctgagccag ccctgtgctc ctccctcccc caacactccc 1381 taccaacccc ctaatcccct actccctcca ccccccctcc actgtaggcc actggatggt 1441 catttgcatc tccgtaaatg tgctctgctc ctcagctgag agagaaaaaa ataaactgta 1501 tttggctgca agaaaaaaaa aaaaaaaaaa aaaa

An exemplary human CD3G amino acid sequence is set forth below (SEQ ID NO: 102; GenBank Accession No: P09693.1, Version 1, incorporated herein by reference):

  1 meqgkglavl ilaiillqgt laqsikgnhl vkvydyqedg svlltcdaea knitwfkdgk  61 migfltedkk kwnlgsnakd prgmyqckgs qnkskplqvy yrmcqnciel naatisgflf 121 aeivsifvla vgvyfiagqd gvrqsrasdk qtllpndqly qplkdreddq yshlqgnqlr 181 rn

An exemplary human CD3G nucleic acid sequence is set forth below (SEQ ID NO: 103; GenBank Accession No: NM_000073.2, Version 2, incorporated herein by reference):

   1 agtctagctg ctgcacaggc tggctggctg gctggctgct aagggctgct ccacgctttt   61 gccggaggac agagactgac atggaacagg ggaagggcct ggctgtcctc atcctggcta  121 tcattcttct tcaaggtact ttggcccagt caatcaaagg aaaccacttg gttaaggtgt  181 atgactatca agaagatggt tcggtacttc tgacttgtga tgcagaagcc aaaaatatca  241 catggtttaa agatgggaag atgatcggct tcctaactga agataaaaaa aaatggaatc  301 tgggaagtaa tgccaaggac cctcgaggga tgtatcagtg taaaggatca cagaacaagt  361 caaaaccact ccaagtgtat tacagaatgt gtcagaactg cattgaacta aatgcagcca  421 ccatatctgg ctttctcttt gctgaaatcg tcagcatttt cgtccttgct gttggggtct  481 acttcattgc tggacaggat ggagttcgcc agtcgagagc ttcagacaag cagactctgt  541 tgcccaatga ccagctctac cagcccctca aggatcgaga agatgaccag tacagccacc  601 ttcaaggaaa ccagttgagg aggaattgaa ctcaggactc agagtagtcc aggtgttctc  661 ctcctattca gttcccagaa tcaaagcaat gcattttgga aagctcctag cagagagact  721 ttcagcccta aatctagact caaggttccc agagatgaca aatggagaag aaaggccatc  781 agagcaaatt tgggggtttc tcaaataaaa taaaaataaa aacaaatact gtgtttcaga  841 agcgccacct attggggaaa attgtaaaag aaaaatgaaa agatcaaata accccctgga  901 tttgaatata attttttgtg ttgtaatttt tatttcgttt ttgtataggt tataattcac  961 atggctcaaa tattcagtga aagctctccc tccaccgcca tcccctgcta cccagtgacc 1021 ctgttgccct cttcagagac aaattagttt ctcttttttt tttttttttt tttttttttg 1081 agacagtctg gctctgtcac ccaggctgaa atgcagtggc accatctcgg ctcactgcaa 1141 cctctgcctc ctgggttcaa gcgattctcc tgcctcagcc tcccgggcag ctgggattac 1201 aggcacacac taccacacct ggctaatttt tgtattttta gtagagacag ggttttgctc 1261 tgttggccaa gctggtctcg aactcctgac ctcaagtgat ccgcccgcct c

An exemplary human LCK amino acid sequence is set forth below (SEQ ID NO: 104; GenBank Accession No: P06239.6, Version 6, incorporated herein by reference):

  1 mgcgcsshpe ddwmenidvc enchypivpl dgkgtllirn gsevrdplvt yegsnppasp  61 lqdnlvialh syepshdgdl gfekgeqlri leqsgewwka gslttggegf ipfnfvakan 121 slepepwffk nlsrkdaerq llapgnthgs fliresesta gsfslsvrdf dqnqgevvkh 181 ykirnldngg fyispritfp glhelvrhyt nasdglctrl srpcqtqkpq kpwwedewev 241 pretlklver lgagqfgevw mgyynghtkv avkslkqgsm spdaflaean lmkqlqhqrl 301 vrlyavvtqe piyiiteyme ngslvdflkt psgikltink lldmaaqiae gmafieerny 361 ihrdlraani lvsdtlscki adfglarlie dneytarega kfpikwtape ainygtftik 421 sdvwsfgill teivthgrip ypgmtnpevi qnlergyrmv rpdncpeely qlmrlcwker 481 pedrptfdyl rsvledffta teggyqpqp

An exemplary human LCK nucleic acid sequence is set forth below (SEQ ID NO: 105; GenBank Accession No: AH002862.2, Version 2, incorporated herein by reference):

   1 gaattcgaac tgttgcccta ctctccaacc atgattaatg ggtgttgtcc tggcctctga   61 ctacagcagg ggccgttact atgccctctt gaagacatga ggttgtcctg tctgcctcct  121 gaaacaggct gttttccagc attctgtctg taagagggat ggtagcctgc cattcaccta  181 cccttgacta taataaagct actgttccat gccctgagat gacatgggaa ttgttctctc  241 ggcctgacct gactgtaaca tgcatggtct gctcaccagc tatttaacag ggatattgtc  301 ctctcctctg actctgatac gatgctacct ttgctgccag acagaaacca aaagggtctc  361 tcagctgcaa ctggtggtgc tgaggtgctg tttgcctctc accataagct gagtgtgtgt  421 ccgcttgccc cctgctcact gggcccaaag gctgcccttg aatctcttgc ccagatgcac  481 cctggagggc agaagggagg gtctatcaga catcctcccc tcaactttaa acctcccagt  541 gtcaccctgg gacagtaggg gaagatggac ctggtctgga gatgtagggg acccccaggg  601 gctgagaggc aggggtctat ggtggcagga agcttggcgt gctagagggt tgtggttggg  661 ctgctggggc ccggttggct gcggagcctc cggaggaggc aggaagtcag ggtgggacgt  721 gggcgcgggg agacaggtgg tggctacgac ggcgaaggga gctgagactg tccaggcagc  781 caggttaggc caggaggacc atgtgaatgg ggccagaggg ctcccgggct gggcaggtaa  841 ggagcgctgg tattgggcgc aggcgccggg gtgagaggcc tgatagcaga cgctgcagnn  901 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn  961 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnngg gactccgggg gcttcaaagt 1021 tgagggcccc acctctgctt cagcgcaaaa caggcacaca tttatcactt tactcctatg 1081 gagttctgct tgatttcatc agacaaaaaa tttccactcc taaaacacgg caaataaaca 1141 aaaaaaaagt tatggccaac cagagtcact ggagggtttt ctcctgggga gaagcaagcc 1201 cgtgtttgaa ggaaccctgt gagatgactg tgggctgtgt gaggggaaca gcgggggctt 1261 gatggtggac ttcgggagca gaagcctctt tctcagcctc ctcagctaga caggggaatt 1321 ataataggag gtgtggcgtg cacacctctc cagtagggga gggtctgata agtcaggtct 1381 ctcccaggct tgggaaagtg tgtgtcatgc tctaggaggt ggtcctccca acacagggta 1441 ctggcagagg gagagggagg gggcagaggc aggaagtggg taactagact aacaaaggtg 1501 cctgtggcgg tttgcccatc ccaggtgggg agggtggggc tagggctcag gggccgtgtg 1561 tgaatttact tgtagcctga gggctcagag ggagcaccgg tttggagctg ggacccccta 1621 ttttagcttt tctgtggctg gtgaatgggg atcccaggat ctcacaatct caggtacttt 1681 tggaactttc cagggcaagg ccccattata tctgatgttg ggggagcaga tcttggggga 1741 gccccttcag ccccctcttc cattccctca gggaccatgg gctgtggctg cagctcacac 1801 ccggaagatg actggatgga aaacatcgat gtgtgtgaga actgccatta tcccatagtc 1861 ccactggatg gcaagggcac ggtaagaggc gagacagggg ccttggtgag ggagttgggt 1921 agagaatgca acccaggaga aagaaatgac cagcacttac aggcccttga aag

An exemplary human T cell receptor alpha amino acid sequence is set forth below (SEQ ID NO: 106; GenBank Accession No: ALC78508.1, Version 1, incorporated herein by reference):

  1 mkslrvllvi lwlqlswvws qgkeveqnsg plsvpegaia slnctysdrg sgsffwyrqy  61 sgkspelims iysngdkedg rftaqlnkas qyvsllirds qpsdsatylc avetsgtyky 121 ifgtgtrlkv laniqnpdpa vyqlrdskss dksvclftdf dsqtnvsgsk dsdvyitdkt 181 vldmrsmdfk snsavawsnk sdfacanafn nsiipedtff pspesscdvk lveksfetdt 241 nlnfqnlsvi gfrilllkva gfnllmtlrl wss

An exemplary human T cell receptor alpha nucleic acid sequence is set forth below (SEQ ID NO: 107; GenBank Accession No: M27377.1, Version 1, incorporated herein by reference):

  1 atggcctctg cacccatctc gatgcttgcg atgctcttca cattgagtgg gctgagagct  61 cagtcagtgg ctcagcggaa gatcaggtca acgttgctga agggaatcct ctgactgtga 121 aatgcaccta ttcagtctct ggaaaccctt atcttttttg gtatgttcaa taccccaacc 181 gaggcctcca gttccttctg aaatacatca caggggataa cctggttaaa ggcagctatg 241 gctttgaagc tgaatttaac aagagccaaa cctccttcca cctgaagaaa ccatctgccc 301 ttgtgagcga ctccgctttg tacttctgtg ctgtgagacc cgacagaggc tcaaccctgg 361 ggaggctata ctttggaaga ggaactcagt tgactgtctg gcctgatatc cagaaccct

An exemplary human T cell receptor beta amino acid sequence is set forth below (SEQ ID NO: 108; GenBank Accession No: CAA39990.1, Version 1, incorporated herein by reference):

  1 vafcllveel ieagvvqspr ykiiekkqpv afwcnpisgh ntlywylqnl gqgpelliry  61 eneeavddsq Lpkdrfsaer lkgvdstlki qpaelgdsav ylcassstgf ntgelffgeg 121 srltvledlk nvfppevavf

An exemplary human T cell receptor beta nucleic acid sequence is set forth below (SEQ ID NO: 109; GenBank Accession No: L06888.1, Version 1, incorporated herein by reference):

  1 atgggctgca ggctgctctg ctgtgcggtt ctctgtctcc tgggagcggt ccccatggaa  61 acgggagtta cgcagacacc aagacacctg gtcatgggaa tgacaaataa gaagtctttg 121 aaatgtgaac aacatctggg tcataacgct atgtattggt acaagcaaag tgctaagaag 181 ccactggagc tcatgtttgt ctacagtctt gaagaacgtg ttgaaaacaa cagtgtgcca 241 agtcgcttct cacctgaatg ccccaacagc tctcacttat tccttcacct acacaccctg 301 cagccagaag actcggccct gtatctctgc gccagcagc

An exemplary human GNLY amino acid sequence is set forth below (SEQ ID NO: 110; GenBank Accession No: CAG46657.1, Version 1, incorporated herein by reference):

  1 matwalllla amllgnpglv fsrlspeyyd larahlrdee kscpclaqeg pqgdlltktq  61 elgrdyrtcl tivqklkkmv dkptqrsysn aatrvcrtgr srwrdvcrnf mrryqsrvtq 121 glvagetaqq icedlrlcip stgpl

An exemplary human GNLY nucleic acid sequence is set forth below (SEQ ID NO: 111; GenBank Accession No: NM_001302758.1, Version 1, incorporated herein by reference):

  1 gtatctgtgg taaacccagt gacacggggg agatgacata caaaaagggc aggacctgag  61  aaagattaag ctgcaggctc cctgcccata aaacagggtg tgaaaggcat ctcagcggct 121 gccccaccat ggctacctgg gccctcctgc tccttgcagc catgctcctg ggcaacccag 181 gccttgaggt cagtgtgagc cccaagggca agaacacttc tggaagggag agtggatttg 241 gctgggccat ctggatggaa ggtctggtct tctctcgtct gagccctgag tactacgacc 301 tggcaagagc ccacctgcgt gatgaggaga aatcctgccc gtgcctggcc caggagggcc 361 cccagggtga cctgttgacc aaaacacagg agctgggccg tgactacagg acctgtctga 421 cgatagtcca aaaactgaag aagatggtgg ataagcccac ccagagaagt gtttccaatg 481 ctgcgacccg ggtgtgtagg acggggaggt cacgatggcg cgacgtctgc agaaatttca 541 tgaggaggta tcagtctaga gttacccagg gcctcgtggc cggagaaact gcccagcaga 601 tctgtgagga cctcaggttg tgtatacctt ctacaggtcc cctctgagcc ctctcacctt 661 gtcctgtgga agaagcacag gctcctgtcc tcagatcccg ggaacctcag caacctctgc 721 cggctcctcg cttcctcgat ccagaatcca ctctccagtc tccctcccct gactccctct 781 gctgtcctcc cctctcacga gaataaagtg tcaagcaaga ttttagccgc agctgcttct 841 tctttggtgg atttgagggg tgggtgtcag tggcatgctg gggtgagctg tgtagtcctt 901 caataaatgt ctgtcgtgtg tccc

An exemplary human GZMA amino acid sequence is set forth below (SEQ ID NO: 112; GenBank Accession No: CAG33249.1, Version 1, incorporated herein by reference):

  1 mrnsyrflas slsvvvslll ipedvcekii ggnevtphsr pymvllsldr kticagalia  61 kdwvltaahc nlnkrsqvil gahsitreep tkqimlvkke fpypcydpat regdlkllql 121 tekakinkyv tilhlpkkgd dvkpgtmcqv agwgrthnsa swsdtlrevn itiidrkvcn 181 drnhynfnpv igmnmvcags lrggrdscng dsgspllceg vfrgvtsfgl enkcgdprgp 241 gvyillskkh lnwiimtikg av

An exemplary human GZMA nucleic acid sequence is set forth below (SEQ ID NO: 113; GenBank Accession No: NM_006144.3, Version 3, incorporated herein by reference):

  1 agattttcag gttgattgat gtgggacagc agccacaatg aggaactcct atagatttct  61 ggcatcctct ctctcagttg tcgtttctct cctgctaatt cctgaagatg tctgtgaaaa 121 aattattgga ggaaatgaag taactcctca ttcaagaccc tacatggtcc tacttagtct 181 tgacagaaaa accatctgtg ctggggcttt gattgcaaaa gactgggtgt tgactgcagc 241 tcactgtaac ttgaacaaaa ggtcccaggt cattcttggg gctcactcaa taaccaggga 301 agagccaaca aaacagataa tgcttgttaa gaaagagttt ccctatccat gctatgaccc 361 agccacacgc gaaggtgacc ttaaactttt acagctgacg gaaaaagcaa aaattaacaa 421 atatgtgact atccttcatc tacctaaaaa gggggatgat gtgaaaccag gaaccatgtg 481 ccaagttgca gggtggggca ggactcacaa tagtgcatct tggtccgata ctctgagaga 541 agtcaatatc accatcatag acagaaaagt ctgcaatgat cgaaatcact ataattttaa 601 ccctgtgatt ggaatgaata tggtttgtgc tggaagcctc cgaggtggaa gagactcgtg 661 caatggagat tctggaagcc ctttgttgtg cgagggtgtt ttccgagggg tcacttcctt 721 tggccttgaa aataaatgcg gagaccctcg tgggcctggt gtctatattc ttctctcaaa 781 gaaacacctc aactggataa ttatgactat caagggagca gtttaaataa ccgtttcctt 841 tcatttactg tggcttctta atcttttcac aaataaaatc aatttgcatg actgtaaaaa 901 aaaaaaaaaa aaa

An exemplary human GZMB amino acid sequence is set forth below (SEQ ID NO: 114; GenBank Accession No: P10144.2, Version 2, incorporated herein by reference):

  1 mqpillllaf lllpradage iiggheakph srpymaylmi wdqkslkrcg gflirddfvl  61 taahcwgssi nvtlgahnik eqeptqqfip vkrpiphpay npknfsndim llqlerkakr 121 travqplrlp snkaqvkpgq tcsvagwgqt aplgkhshtl qevkmtvqed rkcesdlrhy 181 ydstielcvg dpeikktsfk gdsggplvcn kvaqgivsyg rnngmpprac tkvssfvhwi 241 kktmkry

An exemplary human GZMB nucleic acid sequence is set forth below (SEQ ID NO: 115; GenBank Accession No: NM_004131.4, Version 4, incorporated herein by reference):

  1 ccaagagcta aaagagagca aggaggaaac aacagcagct ccaaccaggg cagccttcct  61 gagaagatgc aaccaatcct gcttctgctg gccttcctcc tgctgcccag ggcagatgca 121 ggggagatca tcgggggaca tgaggccaag ccccactccc gcccctacat ggcttatctt 181 atgatctggg atcagaagtc tctgaagagg tgcggtggct tcctgatacg agacgacttc 241 gtgctgacag ctgctcactg ttggggaagc tccataaatg tcaccttggg ggcccacaat 301 atcaaagaac aggagccgac ccagcagttt atccctgtga aaagacccat cccccatcca 361 gcctataatc ctaagaactt ctccaacgac atcatgctac tgcagctgga gagaaaggcc 421 aagcggacca gagctgtgca gcccctcagg ctacctagca acaaggccca ggtgaagcca 481 gggcagacat gcagtgtggc cggctggggg cagacggccc ccctgggaaa acactcacac 541 acactacaag aggtgaagat gacagtgcag gaagatcgaa agtgcgaatc tgacttacgc 601 cattattacg acagtaccat tgagttgtgc gtgggggacc cagagattaa aaagacttcc 661 tttaaggggg actctggagg ccctcttgtg tgtaacaagg tggcccaggg cattgtctcc 721 tatggacgaa acaatggcat gcctccacga gcctgcacca aagtctcaag ctttgtacac 781 tggataaaga aaaccatgaa acgctactaa ctacaggaag caaactaagc ccccgctgta 841 atgaaacacc ttctctggag ccaagtccag atttacactg ggagaggtgc cagcaactga 901 ataaatacct cttagctgag tggaaaaaaa aaaaaaaaaa a

An exemplary human GZMH amino acid sequence is set forth below (SEQ ID NO: 116; GenBank Accession No: P20718.1, Version 1, incorporated herein by reference):

  1 mqpfllllaf lltpgagtee iiggheakph srpymafvqf lqeksrkrcg gilvrkdfvl  61 taahcqgssi nvtlgahnik eqertqqfip vkrpiphpay npknfsndim llqlerkakw 121 ttavrplrlp sskaqvkpgq lcsvagwgyv smstlattlq evlltvqkdc qcerlfhgny 181 srateicvgd pkktqtgfkg dsggplvckd vaqgilsygn kkgtppgvyi kvshflpwik 241 rtmkrl

An exemplary human GZMH nucleic acid sequence is set forth below (SEQ ID NO: 117; GenBank Accession No: NM_033423.4, Version 4, incorporated herein by reference):

  1 gaggtctctg agtttactgt acccatccct ccttcatctc cctccagcat ttgtttctgg  61 aaggagtcaa caccaacagc tctgacctgg gcagccttcc tgagaaaatg cagccattcc 121 tcctcctgtt ggcctttctt ctgacccctg gggctgggac agaggagatc atcgggggcc 181 atgaggccaa gccccactcc cgcccctaca tggcctttgt tcagtttctg caagagaaga 241 gtcggaagag gtgtggcggc atcctagtga gaaaggactt tgtgctgaca gctgctcact 301 gccagggaag ctccataaat gtcaccttgg gggcccacaa tatcaaggaa caggagcgga 361 cccagcagtt tatccctgtg aaaagaccca tcccccatcc agcctataat cctaagaact 421 tctccaacga catcatgcta ctgcagctgg agagaaaggc caagtggacc acagctgtgc 481 ggcctctcag gctacctagc agcaaggccc aggtgaagcc agggcagctg tgcagtgtgg 541 ctggctgggg ttatgtctca atgagcactt tagcaaccac actgcaggaa gtgttgctga 601 cagtgcagaa ggactgccag tgtgaacgtc tcttccatgg caattacagc agagccactg 661 agatttgtgt gggggatcca aagaagacac agaccggttt caagggggac tccggggggc 721 ccctcgtgtg taaggacgta gcccaaggta ttctctccta tggaaacaaa aaagggacac 781 ctccaggagt ctacatcaag gtctcacact tcctgccctg gataaagaga acaatgaagc 841 gcctctaaca gcaggcatga gactaacctt cctctgggcc tgaccatctc tgggacagag 901 gcaagaatcc ccaaggggtg ggcagtcggg gttgcaggac tgtaataaat ggatctctgg 961 tgtaaatatg aaaaaaaaaa aaaaaaa

An exemplary human GZMK amino acid sequence is set forth below (SEQ ID NO: 118; GenBank Accession No: P49863.1, Version 1, incorporated herein by reference):

  1 mtkfssfslf flivgaymth vcfnmeiigg kevsphsrpf masiqygghh vcggvlidpq  61 wvltaahcqy rftkgqsptv vlgahslskn easkqtleik kfipfsrvts dpqsndimlv 121 klqtaaklnk hvkmlhirsk tslrsgtkck vtgwgatdpd slrpsdtlre vtvtvlsrkl 181 cnsqsyyngd pfitkdmvca gdakgqkdsc kgdsggplic kgvfhaivsg ghecgvatkp 241 giytlltkky qtwiksnlvp phtn

An exemplary human GZMK nucleic acid sequence is set forth below (SEQ ID NO: 119; GenBank Accession No: NM_002104.2, Version 2, incorporated herein by reference):

   1 gatcaacaca tttcatctgg gcttcttaaa tctaaatctt taaaatgact aagttttctt   61 ccttttctct gtttttccta atagttgggg cttatatgac tcatgtgtgt ttcaatatgg  121 aaattattgg agggaaagaa gtgtcacctc attccaggcc atttatggcc tccatccagt  181 atggcggaca tcacgtttgt ggaggtgttc tgattgatcc acagtgggtg ctgacagcag  241 cccactgcca atatcggttt accaaaggcc agtctcccac tgtggtttta ggcgcacact  301 ctctctcaaa gaatgaggcc tccaaacaaa cactggagat caaaaaattt ataccattct  361 caagagttac atcagatcct caatcaaatg atatcatgct ggttaagctt caaacagccg  421 caaaactcaa taaacatgtc aagatgctcc acataagatc caaaacctct cttagatctg  481 gaaccaaatg caaggttact ggctggggag ccaccgatcc agattcatta agaccttctg  541 acaccctgcg agaagtcact gttactgtcc taagtcgaaa actttgcaac agccaaagtt  601 actacaacgg cgaccctttt atcaccaaag acatggtctg tgcaggagat gccaaaggcc  661 agaaggattc ctgtaagggt gactcagggg gccccttgat ctgtaaaggt gtcttccacg  721 ctatagtctc tggaggtcat gaatgtggtg ttgccacaaa gcctggaatc tacaccctgt  781 taaccaagaa ataccagact tggatcaaaa gcaaccttgt cccgcctcat acaaattaag  841 ttacaaataa ttttattgga tgcacttgct tcttttttcc taatatgctc gcaggttaga  901 gttgggtgta agtaaagcag agcacatatg gggtccattt ttgcacttgt aagtcatttt  961 attaaggaat caagttcttt ttcacttgta tcactgatgt atttctacca tgctggtttt 1021 attctaaata aaatttagaa gactcaaaaa aaaaaaaaaa aaaaaaaaaa aaaa

An exemplary human PRF1 amino acid sequence is set forth below (SEQ ID NO: 120; GenBank Accession No: P14222.1, Version 1, incorporated herein by reference):

  1 maarllllgi lllllplpvp apchtaarse ckrshkfvpg awlagegvdv tslrrsgsfp  61 vdtqrflrpd gtctlcenal qegtlqrlpl altnwraqgs gcqrhvtrak vssteavard 121 aarsirndwk vgldvtpkpt snvhvsvags hsqaanfaaq kthqdqysfs tdtvecrfys 181 fhvvhtpplh pdfkralgdl phhfnastqp aylrlisnyg thfiravelg grisaltalr 241 tcelaleglt dnevedcltv eaqvnigihg sisaeakace ekkkkhkmta sfhqtyrerh 301 sevvgghhts indllfgiqa gpeqysawvn slpgspglvd ytleplhvll dsqdprreal 361 rralsqyltd rarwrdcsrp cppgrqkspr dpcqcvchgs avttqdccpr qrglaqlevt 421 fiqawglwgd wftatdayvk lffggqelrt stvwdnnnpi wsvrldfgdv llatggplrl 481 qvwdqdsgrd ddllgtcdqa pksgshevrc nlnhghlkfr yharclphlg ggtcldyvpq 541 mllgeppgnr sgavw

An exemplary human PRF1 nucleic acid sequence is set forth below (SEQ ID NO: 121; GenBank Accession No: M31951.1, Version 1, incorporated herein by reference):

   1 gaattccaaa gtcctctctt tgattttata ggtgaggaaa ctaacgctca gaaagggggt   61 tgatatctat cgccgtgagg catacggtaa gtttctggtg aagctgggat cagaacctgt  121 ttagactttg cctctctttt cccgcagata ctttgcagga cttctatgtc cctcaaaccg  181 gccttcctgt catggtcagg aaagaaactc ctcacagcct cagcatccaa gtcaggccat  241 gggtgacagc tggaaagtga tcaggaggct gcagtttcta gaagagggtg gggacactgc  301 ggagagaaga tggggccaga ttccgagaag acagcataag cccctgttcc tgtaagagca  361 gggacggaag cagggacata aacgcaaggg atgagcccca aagtgtgacc catgagacat  421 gatgtcacat gtggtctgga gcctgcccca cttcttccca tcatatacac agttatgaga  481 acaagttgtg agaaccacct cctcccttac ccagctgccc ccaccccaga agccgtgtga  541 ttttgccccc cagtgccctg tgagtcactc cacccatgga aacctcaccc caccctgacc  601 tcaagcaagg cagagtgcag aagacatgtc ctccggtgct accagaccac tctcaccagc  661 acccacgacc tcagcagggc tggagccagc gtggaggcca ctggctgtcc tcacaaagcg  721 aggagcagga gcccctgttc gaggaacatg cttggagttc ggagcctggg ctagggtggg  781 atgtaggttg agcaggaagt ggatggcaag attagagcaa catctctctt ctcccactca  841 gggaggaggg aatggccaca ggctctgaca ctcaagaagg gccaggcaca gttccaagca  901 cttcacaaca acccctaggg tctacatgac ctacaatccc aattgttcag tgaagaaact  961 gaggcacagt gaggctgaag aaccctacca gtccacactg ctggtgcata accgagctgc 1021 ccaagccccg gcggtctggc gtgtaggccc atgctctgag ccgccgcctc tgcttgcctc 1081 ttacatccca cacatgcgat gctgtgcatc agaagcaagg agatggccct gctggcctgt 1141 tcatcaacac cagggccgag tctcaaagtc ctcagcgccc cgccctcctc cgcctgtgtg 1201 ccctgagtcc ccgagcccca gcagctctac tcggcagatg agcctctggc cctgctgctc 1261 gcttcctgag ggctgtcagt ggggagccgg atgagggctg aggacagggt gggtgctcgt 1321 gggaggggag agcacaaagg acctgtgacc acagctgggg gcggggcagg aagtagaagt 1381 gatgtgagtg gtggctggtg caaggagcca cagtgggctg cctggggggc tgatgccacc 1441 attccaggag cctcggtgaa gagaggatat ccatctgtgt agccgcttct ctatacggga 1501 ttccaggtaa ggagagagca gggattgggg gcctggggcc ctgggtggag gggaagaggc 1561 tgatggagca ggaagtgctg tgacctataa gacaagacac ctgggtcaca gacggtgccc 1621 atcactaact cgctgggcag ccctgtgtcc accctgggcc tcagtttcct catgtatgaa 1681 atgaagaggt agcgtgcagt ttctaaggcc ctgcaagtgc tgacattaaa gcttctaaga 1741 aagctggaaa gaggctccct gggacagaat accatgagag tcaggatgag ggctgagttc 1801 actggattag ggttatgact gtgcccgcct cctagctggg atgagcccag ggcctttgaa 1861 gattcccctg gcctctttgc ctccctgggg cgagccacgc tgcctgaaat tccacccttc 1921 aagtcacacc tttgggcagg gcaggaggct ccagctataa tgggggctct ccatagccct 1981 cttgtctcag aacctgtggt acccaagggc aaaggccttt gaagagctca gcttggataa 2041 ggttaggctt gggtaaggtt agagaaagga ggttccagat cataaacagg cccaggcaag 2101 gccccagaaa caccttaaaa ttaggaagaa ccttccagac aatcattgtc catagtaggc 2161 aatagggggg cccctgtcac tgccgaaggc cacagagctt ggcagggagt ggcaaagagg 2221 ggaggggcag caagaaagga tctgaagagc aaccatcgag gcctctcccc acacaaaatc 2281 caagggtgtg gtcaggtctg cccctttttc ttttttttct ttctcttttt tttttttttt 2341 tttttttgag gcagagtctt actctatcac ccaggcggga gtgcagtggt acgatcttgg 2401 ctcactgcaa cctccgcctc ctgggttcaa gcgattctcc tgtctcagcc tcccaagtag 2461 ctgggattac aggcacccgc caccatgccc agctaatttt tgtattttta gtaaagaggg 2521 ggtttcacca cgttggccag gctggtctcg aacttctgac ctccagtgat ccacctgcct 2581 ctgcctccca cagtgttcgg tttacaggtg tgagccacca cacctggcca ggtcggcaga 2641 ttttattcta gaattcgggc tgatgttatt ccataaagct cagagggaga gcgccaaagg 2701 gaaaatgaga agaataggtg caatatagga cctcatttct cttccaattc tgttaagggc 2761 tcagtgggag ggagagaggt tagagagagt gacagagaca aagaaacaga gtgagagtca 2821 gggtgggcaa agggtggctt gttctggggc caaaaatgac acttcttcag aatgaaggct 2881 tcctcaggtc cccagacccc tccctaaacc tgctacagct actctgtccc ctcttctgtg 2941 gccacagccc cctccccacc acccacagtt gtgtcctggg gacagagcca tccacctaga 3001 tccccattag gccttaggga aattctaaaa aggggctccc cttggctggg cttttcccct 3061 ctctgggccc atctgtacaa tgtgggggct gaaccaggcc tataagggac ataccagctc 3121 tgacattcat tgaataatga cttaagagat atctcagccc ctccccttcc atgtgccctg 3181 ataatctgtg gctgtggggg aagggagcag tcatcctcca tccctccacc catggcttcc 3241 cagagcccaa gtgccccctg tctctgcagc tccatggcag cccgtctgct cctcctgggc 3301 atccttctcc tgctgctgcc cctgcccgtc cctgccccgt gccacacagc cgcacgctca 3361 gagtgcaagc gcagccacaa gttcgtgcct ggtgcatggc tggccgggga gggtgtggac 3421 gtgaccagcc tccgccgctc gggctccttc ccagtggaca cacaaaggtt cctgcggccc 3481 gacggcacct gcaccctctg tgaaaatgcc ctacaggagg gcaccctcca gcgcctgcct 3541 ctggcgctca ccaactggcg ggcccagggc tctggctgcc agcgccatgt aaccagggcc 3601 aaagtcagct ccactgaagc tgtggcccgg gatgcggctc gtagcatccg caacgactgg 3661 aaggtcgggc tggacgtgac tcctaagccc accagcaatg tgcatgtgtc tgtggccggc 3721 tcacactcac aggcagccaa ctttgcagcc cagaagaccc accaggacca gtacagcttc 3781 agcactgaca cggtggagtg ccgcttctac aggtgagagc tggggctagg ggtggggggc 3841 tggaaaaggc gcgggaaact ctgggtggtc taagagccct ggaaaggcag agttctccaa 3901 tcaaacttgg aggctgcttc caccaggaag aaactgcaat cctggctctc agacttcagg 3961 tgattcagcc ctgtggcctc ctctcatcca ggaggtccca aatctgggag tgcccagtga 4021 gacatcaagt agagagaaag tgagtgagac catgcctgag agtcccagca gggtgccatt 4081 taggtctagt gagtactgaa ccctgccttt cctgggcaca gccagccttc cacagagtcc 4141 ttcctggata gggacagagg caggagacct ggccgggtca tccttcctca tcgctgtgtg 4201 accttgagca tctcacttct ctctgagctt caatcatcca ctcaaccaat actcacacct 4261 gcctgtggca gggccacact gctgagcgac agcagtcact accctagccc ctgggagtag 4321 gaagtatggg acccatattc cacgtctgag aaaggcacag tgtttgtagg ccagacccaa 4381 gtcacctggt ctgattcatc agacctgggg gccacgtttc ctccacagag aggccgagca 4441 tggcccaagc tgtcaggatc ccgggcatgt gggacccatc cagggggacg gatggatgaa 4501 ggccacatga ctagttccaa agttcgacag ataccatcag tgcaggatca ttgcttttat 4561 gttctttttt actttttctt aaaaaaaaaa tagagatggg gtctcactat gttgcccagg 4621 ctggtctcaa actcctgggc tcaagtgatc ctcccgcctc ggcctcccaa agtgctgggg 4681 ttacaggcat gaaccactgc tcccggccag gatcattgct tttataataa gaaaattaaa 4741 aggaaagaaa aaaatgttat tttgaaaagg aaaagagaaa atacctatac agagcactga 4801 ggtccctgag gggtgagagc ggaggcattc ctgccagccc cgtgccactg tgcttgtgct 4861 ctggagccgg gcccctgggt tccagtccta gttctgccca cttacatgtg accttgagca 4921 gtcctgaagg agttatttga ttgaatgggg gaaatactcc cctgggccca gctgaggtct 4981 ctctcttctc gcagtttcca tgtggtacac actcccccgc tgcaccctga cttcaagagg 5041 gccctcgggg acctgcccca ccacttcaac gcctccaccc agcccgccta cctcaggctt 5101 atctccaact acggcaccca cttcatccgg gctgtggagc tgggtggccg catatcggcc 5161 ctcactgccc tgcgcacctg cgagctggcc ctggaagggc tcacggacaa cgaggtggag 5221 gactgcctga ctgtcgaggc ccaggtcaac ataggcatcc acggcagcat ctctgccgaa 5281 gccaaggcct gtgaggagaa gaagaagaag cacaagatga cggcctcctt ccaccaaacc 5341 taccgggagc gccactcgga agtggttggc ggccatcaca cctccattaa cgacctgctg 5401 ttcgggatcc aggccgggcc cgagcagtac tcagcctggg taaactcgct gcccggcagc 5461 cctggcctgg tggactacac cctggaaccc ctgcacgtgc tgctggacag ccaggacccg 5521 cggcgggagg cactgaggag ggccctgagt cagtacctga cggacagggc tcgctggagg 5581 gactgcagcc ggccgtgccc accagggcgg cagaagagcc cccgagaccc atgccagtgt 5641 gtgtgccatg gctcagcggt caccacccag gactgctgcc ctcggcagag gggcctggcc 5701 cagctggagg tgaccttcat ccaagcatgg ggcctgtggg gggactggtt cactgccacg 5761 gatgcctatg tgaagctctt ctttggtggc caggagctga ggacgagcac cgtgtgggac 5821 aataacaacc ccatctggtc agtgcggctg gattttgggg atgtgctcct ggccacaggg 5881 gggcccctga ggttgcaggt ctgggatcag gactctggca gggacgatga cctccttggc 5941 acctgtgatc aggctcccaa gtctggttcc catgaggtga gatgcaacct gaatcatggc 6001 cacctaaaat tccgctatca tgccaggtgc ttgccccacc tgggaggagg cacctgcctg 6061 gactatgtcc cccaaatgct tctgggggag cctccaggaa accggagtgg ggccgtgtgg 6121 tgagaacagt gagcttggaa aggaccagta tgcttggact gaaggggttc tcacagtggg 6181 agccagggct gtcttcgtat tcccattaga ccaagctt

An exemplary human CD19 amino acid sequence is set forth below (SEQ ID NO: 122; GenBank Accession No: AAB60697.1, Version 1, incorporated herein by reference):

  1 mppprllffl lfltpmevrp eeplvvkveg egdnavlqcl kgtsdgptqq ltwsresplk  61 pflklslglp glgihmrpla swlfifnvsq qmggfylcqp gppsekawqp gwtvnvegsg 121 elfrwnvsdl gglgcglknr ssegpsspsg klmspklyvw akdrpeiweg eppcvpprds 181 lnqslsqdlt mapgstlwls cgvppdsvsr gplswthvhp kgpksllsle lkddrpardm 241 wvmetglllp rataqdagky ychrgnltms fhleitarpv lwhwllrtgg wkvsavtlay 301 lifclcslvg ilhlgralvl rrkrkrmtdp trrffkvtpp pgsgpqnqyg nvlslptpts 361 glgraqrwaa glggtapsyg npssdvqadg algsrsppgv gpeeeegegy eepdseedse 421 fyendsnlgq dqlsqdgsgy enpedeplgp ededsfsnae syenedeelt qpvartmdfl 481 sphgsawdps reatslgsqs yedmrgilya apqlrsirgq pgpnheedad syenmdnpdg 541 pdpawggggr mgtwstr

An exemplary human CD19 nucleic acid sequence is set forth below (SEQ ID NO: 123; GenBank Accession No: M84371.1, Version 1, incorporated herein by reference):

1 ggatcctctc gcctcggcct cctaaagtat tgggattaca ggcatgagcc tctgtgcctg 61 gctgtaactg acatgtttta agcaggggaa tgacatgctc tagtgaaagc cagtctgggc 121 agctgggtag ctaatgaggg gattagagag attttgttga atgaaaggca gattgagtcc 181 tgctactcgc ccccttcatt ccccttcatt catgcctcat tcttccgcct cccagccgcc 241 tcaactggcc aaagggaagt ggaggccctg ccacctgtag ggagggtccc ctggggcttg 301 cccacagcaa acaggaagtc acagcctggt gagatgggcc tgggaatcag ccactgagaa 361 agtgggtctc ttgggtccct gaattctttt tctgagtccc tgcagcagtg aaaaagacac 421 agaggcacat agagagtgac agagaaagag agagacagag aggagaggca tggggcagaa 481 taagaacaga tttaggagtt agaactcctg ggttctttta aaacaatttt tcttttagag 541 acagggtctt gttgtgttgc ccggactgga gcacagtggc tattcccagg cataatcatg 601 gtgcactgca gccttgaact cctgggctca agcgatcctt ctacctcagc ctcccaagga 661 cctgggacca taggcgtgta ccactgtgcc tggcttttgc ctggttttaa actgaggcag 721 tatgacttga gctcttaggc attaattgaa gctgtatctc attaactgag ggcttatgat 781 gtgctggaca ctgggctaat agtgctgaac atattgtcat ttttaatctt cacaaacaat 841 atttgtatag gactgttttc ttttcttttt tttttttgaa acagagtctc actctggtgc 901 ccaggctgga gtgcagtggt gtgatctcgg ctcactgcaa cctccgcctc ctggtttcca 961 gtgattctcc tgcctcagcc tcctaagtag ctgggattac aggtgtgcgc caccatgccc 1021 ggctaatttt tttttttttt tttgagaagg agtctatgtg cccagcattg ttctagagca 1081 cttgcaatta gtggtgaaca acacggtctc tactccaagg ggctcacatt cttgtgcaga 1141 aaacagaaat gaacaaataa acacacaaga tcatttcccg tggtagtgag agctgggatg 1201 aaaataaaac agcgtggcag ggaggaggca agtgttgtga gtctggaggg ttcctggaga 1261 atggggcctg aggcgtgacc accgccttcc tctctggggg gactgcctgc cgcccccgca 1321 gacacccatg gttgagtgcc ctccaggccc ctgcctgccc cagcatcccc tgcgcgaagc 1381 tgggtgcccc ggagagtctg accaccatgc cacctcctcg cctcctcttc ttcctcctct 1441 tcctcacccc catggaagtc aggcccgagg aacctctagt ggtgaaggtg gaaggtatgt 1501 ccaaagggca gaaagggaag ggattgaggc tggaaacttg agttgtggct gggtgtcctt 1561 ggctgagtaa cttaccctct ctgagcctcc attttcttat ttgtaaaatt caggaaaggg 1621 ttggaaggac tctgccggct cctccactcc cagcttttgg agtcctctgc tctataacct 1681 ggtgtgagga gtcggggggc ttggaggtcc cccccaccca tgcccacacc tctctccctc 1741 tctctccaca gagggagata acgctgtgct gcagtgcctc aaggggacct cagatggccc 1801 cactcagcag ctgacctggt ctcgggagtc cccgcttaaa cccttcttaa aactcagcct 1861 ggggctgcca ggcctgggaa tccacatgag gcccctggca tcctggcttt tcatcttcaa 1921 cgtctctcaa cagatggggg gcttctacct gtgccagccg gggcccccct ctgagaaggc 1981 ctggcagcct ggctggacag tcaatgtgga gggcagcggt gagggccggg ctggggcagg 2041 ggcaggagga gagaagggag gccaccatgg acagaagagg tccgcggcca caatggagct 2101 ggagagaggg gctggaggga ttgagggcga aactcggagc taggtgggca gactcctggg 2161 gcttcgtggc ttcagtatga gctgcttcct gtccctctac ctctcactgt cttctctctc 2221 tctgcgggtc tttgtctcta tttatctctg tctttgagtc tctatctctc tccctctcct 2281 gggtgtctct gcatttggtt ctgggtctct tcccagggga gctgttccgg tggaatgttt 2341 cggacctagg tggcctgggc tgtggcctga agaacaggtc ctcagagggc cccagctccc 2401 cttccgggaa gctcatgagc cccaagctgt atgtgtgggc caaagaccgc cctgagatct 2461 gggagggaga gcctccgtgt gtcccaccga gggacagcct gaaccagagc ctcagccagg 2521 gtatggtgat gactggggag atgccgggaa gcgggggtcc agagacagag gggaggggaa 2581 actgaagagg tgaaaccctg aggatcaggc tttccttgtc ttatctctcc ctgtcccaga 2641 cctcaccatg gcccctggct ccacactctg gctgtcctgt ggggtacccc ctgactctgt 2701 gtccaggggc cccctctcct ggacccatgt gcaccccaag gggcctaagt cattgctgag 2761 cctagagctg aaggacgatc gcccggccag agatatgtgg gtaatggaga cgggtctgtt 2821 gttgccccgg gccacagctc aagacgctgg aaagtattat tgtcaccgtg gcaacctgac 2881 catgtcattc cacctggaga tcactgctcg gccaggtaga gtttctctca actgggaggc 2941 atctgtgtgg gggtactggg aagaagtgga agccagtcaa tcttagattc ccccaacccg 3001 agggctactc ccagcctcac cccaaacccc aacttccaca cagaacactg actccaagtc 3061 tttctttttt ttgacagagt ctcgctctgt tgcctaggct ggagtgcagt ggtgccatct 3121 tgtcttggct cactgcaacc tccgcctccc aggttcaagt gattcccctg cctcagcctc 3181 ctgagtagct gggattacag gtgcccacca ccacgcctgg ctaatttttt tttttttttt 3241 gagacggagt cttgcactgt cacccaggct ggagtgcagt ggcacgatct cagctcactg 3301 caacctccac cttccaggtt caagtgattc tcctgcctca gcctcccgag tagctgggat 3361 taaagcctgg ctaatttttt ttgtattttt agtagagatg gggtttcatt atgttggcca 3421 ggctggtctc aaactcctga cctcgtgatc cacccgcctc ggcctcccaa agtgctggga 3481 ttacagacat gagccacagg gccgggccaa gcctaatttt gtatttttag tagagatggg 3541 gtttctccct gttggaccag gctggtcttg aactcctgac ttcaggtgat ctgcctgcct 3601 tggcctccca aagtactggg attacaggca taagccaccg cacctggcct agacttcaag 3661 tctttcttcc ctcgcttcca agacactact tttctgggtc ttcacctacc attgcttgcg 3721 cctgcccacc agcttgggtg gagtcttcct tcctccccaa ctcctcactc ttggagccct 3781 gggccctctt cttatccctg tctgcacact ttcctatttg aacttgactc tcaatggctt 3841 cttgggtcac catgccttgg tgactctatt ccaggctcca tactcagcca tctcctgtgc 3901 catttgatat cccatggaca cctcaggctc aacagataca aaatcaaact caatgtcttc 3961 cccaagtata gtcttcttgg tggcccagtg taagcagagg gcaccaccac ctgctccctc 4021 gcccaggcta agaacctggg catccttctt tttcctcacc ccgtccaaca aactggtcac 4081 agtgttctgc caattctctc tccatgcaat cctatcatgc tatcctaact gcaattcaca 4141 aacccaaccc caactttcac tccaaacttg atccaagcaa tgtgctggat cccaactgta 4201 accttgcaaa ctcaactctg cccttcactt tgaccgtgac tatccttaat tgcagcagga 4261 aactgatcat tatgctcccc tcaatccaca cattgcctct gagtacagcc atggtttgtc 4321 cacgatttgc tcaaagacac tgcccatgtc ctgtgccagg gtctgtgaca atccctgacc 4381 tcctgggaca tggctcctta gagagaggag agcctttctc acagcttggg actttgagtc 4441 tgtgtctttt tttttttctt gagacggagt tttgctgtgg ttgcccaggc tggagtgcag 4501 tgatctcggc tcactgaaac ctccgcctcc cgggttcaaa cgattctcct gcctcagcct 4561 cccaagtagc tgggattaca ggcacccacc accatgccca gctaattttt ttgtattttt 4621 agtagagatg gggtttcacc atgttggcca ggctggtctc gaactcctga cctcaggtga 4681 tccacccgcc tttgcctccc aaagtgctgg gattacaggc gtcaaccacc gcgcccggcc 4741 gagtctgtgt cttgcctctg tgcctcagac ttgcggttcc ttgagatctc aggattggga 4801 cgtaagatgc cagcctgggg tcctcgtctc atagcccctt ccccctagta ctatggcact 4861 ggctgctgag gactggtggc tggaaggtct cagctgtgac tttggcttat ctgatcttct 4921 gcctgtgttc ccttgtgggc attcttcatc ttcaaagagg tgagtcatgt ccccagtggg 4981 tctgtccaaa ccctactcca tcttccccag gataagccgg ctctggccag tctgacaacc 5041 atctttcttt cctcccatcc ctcccttcaa gaccccagaa tcctgttctc cccagtcttc 5101 ctctagcctc cctcaaactt cccaagcctc ttgcaatttt tttttttttt ttgagacagg 5161 gtctcattct gtcaccccag ctggagtgca gtggcacaat ctgagctcac tgtaacctct 5221 gcctcccagg cttaagtgat tcttgtgctt cagcctcccg agtacctggg actacaagtg 5281 tatgccacca cacccggcca attttttata tttttagtag agacgaggtt tcaccatgtt 5341 ggccagactg gtctcgaact cttgacctca aatgatccgc ccacctcggc ctcccaaagt 5401 gctgggatta caggcacgag ccaccgcgcc cgtccgcctc gcaatttgaa ctcctgtctc 5461 ctttgttgaa ccaagtgacc tccccagcac ctggccccac aaatcctcac cctgccaagc 5521 agcccctcct ctgatcacgc cctttaactc ccaccagccc tggtcctgag gaggaaaaga 5581 aagcgaatga ctgaccccac caggaggtaa tgcaaccagt gcaccccgcg gtaacaccct 5641 ccaccttcac tttatgcctt gcacttactg tttcctctgc ccaggggttc tttgctccgt 5701 ctctactgtt tcaaatactg cccaacctca aagcccagct ccaaagctac ctcctctgtg 5761 aagaactcct tggaaatgat catctcagac tcctctattg gctgtcccag cacaagtgat 5821 cacgtttaac ttctgaaggc ctggacagaa tcttgagtgg gtccgccatt ccattccaag 5881 tcggccctca ccgtgcactt cctcttctcc cgccagattc ttcaaagtga cgcctccccc 5941 aggaagcggg ccccagaacc agtacgggaa cgtgctgtct ctccccacac ccacctcagg 6001 cctcggtaag aggcaccgcc cctccagcct atagctccgc cccagatccg gggctccacc 6061 cccactctcc tcatccctcc aatccgctgt gcgccaagcc ttctggagct cggaactccg 6121 cccccggggc ggggagtccc gcccagctat gagccccgcc tctagaacca gaccccgcct 6181 ccagggctca gagccacgcc cccaggaccc agagcctgaa gtcgtaatca agagcagaac 6241 ttcgccccag aactgaaggc ctcggcccta gatttagatt ccgccccagg gttcaaggcc 6301 gggttcctag acccagagtc cattcgcaga gcccaaaaca tcctcttccc gtgccccgcc 6361 gcgcggaccc ttagccttga ccgcccccat ctcttctgac cccgtcttac aatgcccctc 6421 tcaccaggac gcgcccagcg ttgggccgca ggcctggggg gcactgcccc gtcttatgga 6481 aacccgagca gcgacgtcca ggcggatgga gccttggggt cccggagccc gccgggagtg 6541 ggtgaatgac tgggagaggg aagggtcgtt ccccacatgg agggggttgg agcggtctgt 6601 ggcccgaata gtggactggg ccctggagga gagggggcat gactcggttc cccatcccca 6661 tccccaaacc cccaggccca gaagaagagg aaggggaggg ctatgaggaa cctgacagtg 6721 aggaggactc cgagttctat gagaacgact ccaaccttgg gcaggaccag ctctcccagg 6781 gtaaggctgc cctcccccgt ggccccccac ctctgcggtg gcctgtggac tcccatggac 6841 acccctcctt ctacaccaga tggcagcggc tacgagaacc ctgaggatga gcccctgggt 6901 cctgaggatg aagactcctt ctccaacggt aacttggggc ctttgtggga cctcagagac 6961 ttaggtgtaa ttgcagcgct gtgacactcc tagaagggga tccctggagt tctctctctt 7021 ctgccacagc tgagtcttat gagaacgagg atgaagagct gacccagccg gtcgccagga 7081 caatgggtgt gtgtgaggat ggcaacagtc caggggggag gcggaggaca cctggaggcc 7141 aggaggaata gtaacctccc tcttcccttt ccagacttcc tgagccctca tgggtcagcc 7201 tgggacccca gccgggaagc aacctccctg ggtgagagat gctttcaatc agactgcctt 7261 gcccagcttg ggtgacctgg cctcagctct gacaccagat ccaactttga cctgaccctg 7321 accccaaacc cgaacccaat cctgtgactc ctctcacctc aacactgagc cccatccccc 7381 atcctgagcc ccatccccca tcctgacccc caatatttac cccctcccta actgtgaata 7441 tcaacaccga tcccaatgca gtatcagcct ggacttgatc tccacctcac ctcagcccca 7501 gtgcagacct caacttggac cccagcttac tctgcagctt cttcatgact ctgactccga 7561 ctccctccag tttcttcttt ttctttttct tttttttgag acggagtctc cctctgttgc 7621 ccaggctgga gtgcagttgc cacctctgcc tcctaggttc aagcgattct catgcctcag 7681 cctcctgagt agctgggatt atagacgttt gccaccacac ctggctaatt tttgtatttt 7741 cagtagagac agggtttcgc catgttggcc agactggtct ccaactcctg gcctctagtg 7801 atctgcccgc ctttggcttc ccaaagtgct gggattacag gcatgagcca ccacgcccag 7861 cccagttctg ttcttgaccc cttccttagc cataatctaa cccatatcta accctgaccc 7921 tacagctaac tggggcccca aactcaatgc taaccaaatc accccttccc agcacagcat 7981 gggtaatgct cctcaccttc ctctgcccct cagtcttcct ccttaccgta ggctgtactt 8041 cccatgccct agcctccaat tctccatccc ccgcccaagc agggtcccag tcctatgagg 8101 atatgagagg aatcctgtat gcagcccccc agctccgctc cattcggggc cagcctggac 8161 ccaatcatga ggaaggtggg tgcttctgcc gctgtcccct gctgtcccct gggctgactt 8221 tgccttccag cctacttcca gtgccaccca tgttctcctc ctccctggtc ctatccagat 8281 gcagactctt atgagaacat ggataatccc gatgggccag acccagcctg gggaggaggg 8341 ggccgcatgg gcacctggag caccaggtga tcctcaggtg gccaggtgag ctgggactgc 8401 ccctagggaa agcggggagg gagggagata ggcacggatg gcagtggctg ctggctttca 8461 gggagggaga gggaacaggg ttcctagggc ctggtgggca gggggaggac tgctggaccc 8521 ctccccatca ccgtttcttc tgcatagcct ggatctcctc aagtccccaa gattcacacc 8581 tgactctgaa atctgaagac ctcgagcaga tgatgccaac ctctggagca atgttgctta 8641 ggatgtgtgc atgtgtgtaa gtgtgtgtgt gtgtgtgtgt gtgtatacat gccagtgaca 8701 cttccagtcc cctttgtatt ccttaaataa actcaatgag ctc

An exemplary human CD72 amino acid sequence is set forth below (SEQ ID NO: 124; GenBank Accession No: NP_001773.1, Version 1, incorporated herein by reference):

1 maeaityadl rfvkaplkks issrlgqdpg adddgeitye nvqvpavlgv psslassvlg 61 dkaavkseqp taswravtsp avgrilpcrt tclrylllgl lltclllgvt aiclgvrylq 121 vsqqlqqtnr vlevtnsslr qqlrlkitql gqsaedlqgs rrelaqsqea lqveqrahqa 181 aegqlqacqa drqktketlq seeqqrrale qklsnmenrl kpfftcgsad tccpsgwimh 241 qkscfyislt sknwqesqkq cetlssklat fseiypqshs yyflnsllpn ggsgnsywtg 301 lssnkdwklt ddtqrtrtya gsskcnkvhk twswwtlese scrsslpyic emtafrfpd

An exemplary human CD72 nucleic acid sequence is set forth below (SEQ ID NO: 125; GenBank Accession No: NM_001782.2, Version 2, incorporated herein by reference):

1 aattgctaag ccgtgcagtc acagagggaa cacagagcct agttgtaaac ggacagagac 61 gagaggggca agggaggaca gtggatgaca gggaagacga gtgggggcag agctgctcag 121 gaccatggct gaggccatca cctatgcaga tctgaggttt gtgaaggctc ccctgaagaa 181 gagcatctcc agccggttag gacaggaccc aggggctgat gatgatgggg aaatcaccta 241 cgagaatgtt caagtgcccg cagtcctagg ggtgccctca agcttggctt cttctgtact 301 aggggacaaa gcagcggtca agtcggagca gccaactgcg tcctggagag ccgtgacgtc 361 accagctgtc gggcggattc tcccctgccg cacaacctgc ctgcgatacc tcctgctcgg 421 cctgctcctc acctgcctgc tgttaggagt gaccgccatc tgcctgggag tgcgctatct 481 gcaggtgtct cagcagctcc agcagacgaa cagggttctg gaagtcacta acagcagcct 541 gaggcagcag ctccgcctca agataacgca gctgggacag agtgcagagg atctgcaggg 601 gtccaggaga gagctggcgc agagtcagga agcactacag gtggaacaga gggctcatca 661 ggcggccgaa gggcagctac aggcctgcca ggcagacaga cagaagacga aggagacctt 721 gcaaagtgag gagcaacaga ggagggcctt ggagcagaag ctgagcaaca tggagaacag 781 actgaagccc ttcttcacat gcggctcagc agacacctgc tgtccgtcgg gatggataat 841 gcatcagaaa agctgctttt acatctcact tacttcaaaa aattggcagg agagccaaaa 901 acaatgtgaa actctgtctt ccaagctggc cacattcagt gaaatttatc cacaatcaca 961 ctcttactac ttcttaaatt cactgttgcc aaatggtggt tcagggaatt catattggac 1021 tggcctcagc tctaacaagg attggaagtt gactgatgat acacaacgca ctaggactta 1081 tgctcaaagc tcaaaatgta acaaggtaca taaaacttgg tcatggtgga cactggagtc 1141 agagtcatgt agaagttctc ttccctacat ctgtgagatg acagctttca ggtttccaga 1201 ttaggacagt cctttgcact gagttgacac tcatgccaac aagaacctgt gcccctcctt 1261 cctaacctga ggcctggggt tcctcagacc atctccttca ttctgggcag tgcccagcca 1321 ccggctgacc cacacctgac acttccagcc agtctgctgc ctgctccctc ttcctgaaac 1381 tggactgttc ctgggaaaag ggtgaagcca cctctagaag ggactttggc ctccccccaa 1441 gaacttccca tggtagaatg gggtggggga ggagggcgca cgggctgagc ggataggggc 1501 ggcccggagc cagccaggca gttttattga aatcttttta aataattg

An exemplary human FCRL1/3 amino acid sequence is set forth below (SEQ ID NO: 126; GenBank Accession No: Q96LA6.1, Version 1, incorporated herein by reference):

1 mlprllllic aplcepaelf liaspshpte gspvtltckm pflqssdaqf qfcffrdtra 61 lgpgwssspk lqiaamwked tgsywceaqt maskvlrsrr sqinvhrvpv advsletqpp 121 ggqvmegdrl vlicsvamgt gditflwykg avglnlqskt qrsltaeyei psvresdaeq 181 yycvaengyg pspsglvsit vripvsrpil mlrapraqaa vedvlelhce alrgsppily 241 wfyheditlg srsapsggga sfnlslteeh sgnysceann glgaqrseav tlnftvptga 301 rsnhltsgvi egllstlgpa tvallfcygl krkigrrsar dplrslpspl pqeftylnsp 361 tpgqlqpiye nvnvvsgdev yslayynqpe qesvaaetlg thmedkvsld iysrlrkani 421 tdvdyedam

An exemplary human FCRL1/3 nucleic acid sequence is set forth below (SEQ ID NO: 127; GenBank Accession No: NM_052938.4, Version 4, incorporated herein by reference):

1 aacttccgat atcaacttcc tcaaacctct gatgagctgc tgctgctcga ctctgaggtg 61 cattcttttt ttgatgagag gcatctctag gtaccatccc tgacctggtc ctcatgctgc 121 cgaggctgtt gctgttgatc tgtgctccac tctgtgaacc tgccgagctg tttttgatag 181 ccagcccctc ccatcccaca gaggggagcc cagtgaccct gacgtgtaag atgccctttc 241 tacagagttc agatgcccag ttccagttct gctttttcag agacacccgg gccttgggcc 301 caggctggag cagctccccc aagctccaga tcgctgccat gtggaaagaa gacacagggt 361 catactggtg cgaggcacag acaatggcgt ccaaagtctt gaggagcagg agatcccaga 421 taaatgtgca cagggtccct gtcgctgatg tgagcttgga gactcagccc ccaggaggac 481 aggtgatgga gggagacagg ctggtcctca tctgctcagt tgctatgggc acaggagaca 541 tcaccttcct ttggtacaaa ggggctgtag gtttaaacct tcagtcaaag acccagcgtt 601 cactgacagc agagtatgag attccttcag tgagggagag tgatgctgag caatattact 661 gtgtagctga aaatggctat ggtcccagcc ccagtgggct ggtgagcatc actgtcagaa 721 tcccggtgtc tcgcccaatc ctcatgctca gggctcccag ggcccaggct gcagtggagg 781 atgtgctgga gcttcactgt gaggccctga gaggctctcc tccgatcctg tactggtttt 841 atcacgagga tatcaccctg gggagcaggt cggccccctc tggaggagga gcctccttca 901 acctttccct gactgaagaa cattctggaa actactcctg tgaggccaac aatggcctgg 961 gggcccagcg cagtgaggcg gtgacactca acttcacagt gcctactggg gccagaagca 1021 atcatcttac ctcaggagtc attgaggggc tgctcagcac ccttggtcca gccaccgtgg 1081 ccttattatt ttgctacggc ctcaaaagaa aaataggaag acgttcagcc agggatccac 1141 tcaggagcct tcccagccct ctaccccaag agttcaccta cctcaactca cctaccccag 1201 ggcagctaca gcctatatat gaaaatgtga atgttgtaag tggggatgag gtttattcac 1261 tggcgtacta taaccagccg gagcaggaat cagtagcagc agaaaccctg gggacacata 1321 tggaggacaa ggtttcctta gacatctatt ccaggctgag gaaagcaaac attacagatg 1381 tggactatga agatgctatg taaggttatg gaagattctg ctctttgaaa accatccatg 1441 accccaagcc tcaggcctga tatgttcttc agagatcctg gggcattagc tttccagtat 1501 acctcttctg gatgccattc tccatggcac tattccttca tctactgtga agtgaagttg 1561 gcgcagccct gaagaaacta cctaggagaa ctaatagaca caggagtgac agggactttg 1621 ttatcagaac cagattcctg ccggctcctt tgaaaacagg tcatattgtg ctcttctgtt 1681 tacaagagga aacaagatgg aataaaagaa attgggatct tgggttggag ggacagtgaa 1741 gcttagagca catgaactca aggttagtga ctctgcagga cttcacagag agagctgtgc 1801 ccatcattca gtccaagtgc tttctctgcc cagacagcac agaactccag ccccgctact 1861 tacatggatc atcgagtttc cacctaaaat atgattctat ttattttgag tcactgttac 1921 caaattagaa ctaaaacaaa gttacataaa aagttattgt gactccactt aattttagtg 1981 acgtattttt gtatatatag gccaacctat accacatcca aaattatgta tctattacag 2041 cccctagaag ctttataaat acagtgtgtc ttcttttatt cacaaaattt ttgaaatcgt 2101 ggtaatatgg tttgaaacct gtatcttaat tatttttttt ttaaattgag acagggtctc 2161 actctgtcac tcaatctgga atgcagtggc acaatcttgc ctcactgcaa cgcctgcctc 2221 tcaggctcaa gcaaacctct cacctcagcc tgctgagtag ctgggactac aggcacatgc 2281 caccaaactt ggccattttt tgtcttacgt agagacaaga tttcaccgtt ttgcccaggc 2341 tggtctcaaa ctcctgggct caagcaatgt attgaatttt aaaataacca ggcactcact 2401 cttatgaatt aataaacatt tggaggtata taaagtaaaa agttaaagtc tttcctgtaa 2461 gttaacacaa atgttaacta ttgttaaaaa ctttacaggt agctctctag atatttttct 2521 atttttgtat gtatacttat gcatacatgt aagtatataa acatttagaa gtgtacctat 2581 ctaacaaact attatgaaat actttcaaat ctgtaaatag atctattata ctattttaaa 2641 agtctctata gtagtgtgtt atatagataa atcataactt ttttcttttt ttattgtagt 2701 aaatatgcac aacataaaat tgatcatttt aaccattttt aagtgtacaa ttcagtggca 2761 ttaagtacta tcataatata ttttaatcct tctcatcact ggtggacatt aaggagactc 2821 tcaaaaaatt catattataa aaacaaagtt caaacaaatg tctttgtact agcatattat 2881 ggcactcctg ctggattatc tgaaggataa atttgtaaat ctagtattgc tagattatgc 2941 atattaaata ttcttgttaa atagtcttca atgtctctca ggtaaggctg tatcaattta 3001 tatcttcacc aacaacgtct gggaaatcag tttgtggggt gtattactta gttttcacat 3061 tgctaataaa gacatatcca agactgggta atttataaaa aaaaaaaaaa aaaaaa

An exemplary human MS4A1 amino acid sequence is set forth below (SEQ ID NO: 128; GenBank Accession No: P11836.1, Version 1, incorporated herein by reference):

1 mttprnsvng tfpaepmkgp iamqsgpkpl frrmsslvgp tqsffmresk tlgavqimng 61 lfhialggll mipagiyapi cvtvwyplwg gimyiisgsl laateknsrk clvkgkmimn 121 slslfaaisg milsimdiln ikishflkme slnfirahtp yiniyncepa npseknspst 181 qycysiqslf lgilsvmlif affqelviag ivenewkrtc srpksnivll saeekkeqti 241 eikeevvglt etssqpknee dieiipiqee eeeetetnfp eppqdqessp iendssp

An exemplary human MS4A1 nucleic acid sequence is set forth below (SEQ ID NO: 129; GenBank Accession No: NM_152866.2, Version 2, incorporated herein by reference):

1 gtctatcagc gatttcatct tcaggcctgg actacaccac tcaccctccc agtgtgcttg 61 agaaacaaac tgcacccact gaactccgca gctagcatcc aaatcagccc ttgagatttg 121 aggccttgga gactcagatc ctgaacaaga gagaacaaaa tctctacttt gatggaactt 181 ccattctgtg gggaagagac tgacaataag caattaaata aataagaact cagcagtagg 241 ccttgcctca gatccaaggt cactcggaag aggccatgtc taccctcaat gacactcatg 301 gaggaaatgc tgagagaagc attcagatgc atgacacaag gtaagactgc caaaaatctt 361 gttcttgctc tcctcatttt gttatttgtt ttatttttag gagttttgag agcaaaatga 421 caacacccag aaattcagta aatgggactt tcccggcaga gccaatgaaa ggccctattg 481 ctatgcaatc tggtccaaaa ccactcttca ggaggatgtc ttcactggtg ggccccacgc 541 aaagcttctt catgagggaa tctaagactt tgggggctgt ccagattatg aatgggctct 601 tccacattgc cctggggggt cttctgatga tcccagcagg gatctatgca cccatctgtg 661 tgactgtgtg gtaccctctc tggggaggca ttatgtatat tatttccgga tcactcctgg 721 cagcaacgga gaaaaactcc aggaagtgtt tggtcaaagg aaaaatgata atgaattcat 781 tgagcctctt tgctgccatt tctggaatga ttctttcaat catggacata cttaatatta 841 aaatttccca ttttttaaaa atggagagtc tgaattttat tagagctcac acaccatata 901 ttaacatata caactgtgaa ccagctaatc cctctgagaa aaactcccca tctacccaat 961 actgttacag catacaatct ctgttcttgg gcattttgtc agtgatgctg atctttgcct 1021 tcttccagga acttgtaata gctggcatcg ttgagaatga atggaaaaga acgtgctcca 1081 gacccaaatc taacatagtt ctcctgtcag cagaagaaaa aaaagaacag actattgaaa 1141 taaaagaaga agtggttggg ctaactgaaa catcttccca accaaagaat gaagaagaca 1201 ttgaaattat tccaatccaa gaagaggaag aagaagaaac agagacgaac tttccagaac 1261 ctccccaaga tcaggaatcc tcaccaatag aaaatgacag ctctccttaa gtgatttctt 1321 ctgttttctg tttccttttt taaacattag tgttcatagc ttccaagaga catgctgact 1381 ttcatttctt gaggtactct gcacatacgc accacatctc tatctggcct ttgcatggag 1441 tgaccatagc tccttctctc ttacattgaa tgtagagaat gtagccattg tagcagcttg 1501 tgttgtcacg cttcttcttt tgagcaactt tcttacactg aagaaaggca gaatgagtgc 1561 ttcagaatgt gatttcctac taacctgttc cttggatagg ctttttagta tagtattttt 1621 ttttgtcatt ttctccatca acaaccaggg agactgcacc tgatggaaaa gatatatgac 1681 tgcttcatga cattcctaaa ctatcttttt tttattccac atctacgttt ttggtggagt 1741 cccttttgca tcattgtttt aaggatgata aaaaaaaata acaactaggg acaatacaga 1801 acccattcca tttatctttc tacagggctg acattgtggc acattcttag agttaccaca 1861 ccccatgagg gaagctctaa atagccaaca cccatctgtt ttttgtaaaa acagcatagc 1921 ttatacatgg acatgtctct gccttaactt ttcctaactc ccactctagg ctattgtttg 1981 catgtctacc tacttttagc cattatgcga gaaaagaaaa aaatgaccat agaaaatgcc 2041 accatgaggt gcccaaattt caaataataa ttaacattta gttatattta taatttccag 2101 atgacaaagt atttcatcaa ataacttcat ttgatgttcc atgatcaaga aagaatccct 2161 atctctattt tacaagtaat tcaaagaggc caaataactt gtaaacaaga aaaggtaact 2221 tgtcaacagt cataactagt aattatgaga gccttgtttc ataaccaggt cttcttactc 2281 aaatcctgtg atgtttgaaa taaccaaatt gtctctccaa tgtctgcata aactgtgaga 2341 gccaagtcaa cagcttttat caagaattta ctctctgacc agcaataaac aagcactgag 2401 agacacagag agccagattc agattttacc catggggata aaaagactca gactttcacc 2461 acatttggaa aactacttgc atcataaata tataataact ggtagtttat atgaagcaga 2521 cactaagtgc tatagacact ctcagaatat catacttgga aacaatgtaa ttaaaatgcc 2581 gaatctgagt caacagctgc cctacttttc aattcagata tactagtacc ttacctagaa 2641 ataatgttaa cctagggtga agtcactata atctgtagtc tattatttgg gcatttgcta 2701 catgatgagt gctgccagat tgtggcaggt aaagagacaa tgtaatttgc actccctatg 2761 atatttctac atttttagcg accactagtg gaagacattc cccaaaatta gaaaaaaagg 2821 agatagaaga tttctgtcta tgtaaagttc tcaaaatttg ttctaaatta ataaaactat 2881 ctttgtgttc ttttctgcaa cagatgattc caacatgggt gtttgtctat tcttctttac 2941 tcttgaaaca ttagaccatg ggaggctctt acagccttga gttgatattt atacaaccca 3001 aatctaggtt tgaacggtga ggtgtcaggt catcaaatat tcatgtctat atagtcttac 3061 acaggttctc aaaaaaaatg ttcatgggat aggtcattga taatggattc cttattctga 3121 gaactccaga cgactgaaat atatgagaga aggaaaagga catagtagga gcaggcctga 3181 gaaaaaaatg aaagtcagaa atctttaaaa aaatacaaga tcttatttct atcttatttt 3241 ttctcctctt ctgaaatata tatgaggatt cctctccaaa cccatggttt ctctaagaat 3301 tttgagtcat ttgtatgacc tcaaataatt agttttagct gacctcacat aactccttat 3361 aataggagac atctttaatg tctgctatta aagaaggatg aaaattccta tgaccttctc 3421 cccgattatc cctttggcaa tatagagtca aataataaca ttgaccaata gtaaacatgc 3481 tttgccaaga agtagaagat atattctcta gccttagttt ttcctcccaa tttgcatttt 3541 tgtaaaaata atgttgtatc cacaaaggaa ataaacttta aaaacccaag tgca

An exemplary human CTLA4 amino acid sequence is set forth below (SEQ ID NO: 130; GenBank Accession No: AAL07473.1, Version 1, incorporated herein by reference):

1 maclgfqrhk aqlnlatrtw pctllffllf ipvfckamhv aqpavvlass rgiasfvcey 61 aspgkatevr vtvlrqadsq vtevcaatym mgneltfldd sictgtssgn qvnltiqglr 121 amdtglyick velmypppyy lgigngtqiy vidpepcpds dfllwilaav ssglffysfl 181 ltavslskml kkrsplttgv yvkmpptepe cekqfqpyfi pin

An exemplary human CTLA4 nucleic acid sequence is set forth below (SEQ ID NO: 131; GenBank Accession No: AF414120.1, Version 1, incorporated herein by reference):

1 cttctgtgtg tgcacatgtg taatacatat ctgggatcaa agctatctat ataaagtcct 61 tgattctgtg tgggttcaaa cacatttcaa agcttcagga tcctgaaagg ttttgctcta 121 cttcctgaag acctgaacac cgctcccata aagccatggc ttgccttgga tttcagcggc 181 acaaggctca gctgaacctg gctaccagga cctggccctg cactctcctg ttttttcttc 241 tcttcatccc tgtcttctgc aaagcaatgc acgtggccca gcctgctgtg gtactggcca 301 gcagccgagg catcgccagc tttgtgtgtg agtatgcatc tccaggcaaa gccactgagg 361 tccgggtgac agtgcttcgg caggctgaca gccaggtgac tgaagtctgt gcggcaacct 421 acatgatggg gaatgagttg accttcctag atgattccat ctgcacgggc acctccagtg 481 gaaatcaagt gaacctcact atccaaggac tgagggccat ggacacggga ctctacatct 541 gcaaggtgga gctcatgtac ccaccgccat actacctggg cataggcaac ggaacccaga 601 tttatgtaat tgatccagaa ccgtgcccag attctgactt cctcctctgg atccttgcag 661 cagttagttc ggggttgttt ttttatagct ttctcctcac agctgtttct ttgagcaaaa 721 tgctaaagaa aagaagccct cttacaacag gggtctatgt gaaaatgccc ccaacagagc 781 cagaatgtga aaagcaattt cagccttatt ttattcccat caattgagaa accattatga 841 agaagagagt ccatatttca atttccaaga gctgaggcaa ttctaacttt tttgctatcc 901 agctattttt atttgtttgt gcatttgggg ggaattcatc tctctttaat ataaagttgg 961 atgcggaacc caaattacgt gtactacaat ttaaagcaaa ggagtagaaa gacagagctg 1021 ggatgtttct gtcacatcag ctccactttc agtgaaagca tcacttggga ttaatatggg 1081 gatgcagcat tatgatgtgg gtcaaggaat taagttaggg aatggcacag cccaaagaag 1141 gaaaaggcag ggagcgaggg agaagactat attgtacaca ccttatattt acgtatgaga 1201 cgtttatagc cgaaatgatc ttttcaagtt aaattttatg ccttttattt cttaaacaaa 1261 tgtatgatta catcaaggct tcaaaaatac tcacatggct atgttttagc cagtgatgct 1321 aaaggttgta ttgcatatat acatatatat atatatatat atatatatat atatatatat 1381 atatatatat tttaatttga tagtattgtg catagagcca cgtatgtttt tgtgtatttg 1441 ttaatggttt gaatataaac actatatggc agtgtctttc caccttgggt cccagggaag 1501 ttttgtggag gagctcagga cactaataca ccaggtagaa cacaaggtca tttgctaact 1561 agcttggaaa ctggatgagg tcatagcagt gcttgattgc gtggaattgt gctgagttgg 1621 tgttgacatg tgctttgggg cttttacacc agttcctttc aatggtttgc aaggaagcca 1681 cagctggtgg tatctgagtt gacttgacag aacactgtct tgaagacaat ggcttactcc 1741 aggagaccca caggtatgac cttctaggaa gctccagttc gatgggccca attcttacaa 1801 acatgtggtt aatgccatgg acagaagaag gcagcaggtg gcagaatggg gtgcatgaag 1861 gtttctgaaa attaacactg cttgtgtttt taactcaata ttttccatga aaatgcaaca 1921 acatgtataa tatttttaat taaataaaaa tctgtggtgg tcgttttaaa aaaaaaaaaa 1981 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaa

An exemplary human LAG3 amino acid sequence is set forth below (SEQ ID NO: 132; GenBank Accession No: AAH52589.1, Version 1, incorporated herein by reference):

1 mweaqflgll flqplwvapv kplqpgaevp vvwaqegapa qlpcsptipl qdlsllrrag 61 vtwqhqpdsg ppaaapghpl apgphpaaps swgprprryt vlsvgpgglr sgrlplqprv 121 qldergrqrg dfslwlrpar radageyraa vhlrdralsc rlrlrlgqas mtasppgslr 181 asdwvilncs fsrpdrpasv hwfrnrgqgr vpvresphhh laesflflpq vspmdsgpwg 241 ciltyrdgfn vsimynltvl glepptpltv yagagsrvgl pcrlpagvgt rsfltakwtp 301 pgggpdllvt gdngdftlrl edvsqaqagt ytchihlqeq qlnatvtlai itgqpqvgke

An exemplary human LAG3 nucleic acid sequence is set forth below (SEQ ID NO: 133; GenBank Accession No: NM_002286.5, Version 5, incorporated herein by reference):

1 acaggggtga aggcccagag accagcagaa cggcatccca gccacgacgg ccactttgct 61 ctgtctgctc tccgccacgg ccctgctctg ttccctggga cacccccgcc cccacctcct 121 caggctgcct gatctgccca gctttccagc tttcctctgg attccggcct ctggtcatcc 181 ctccccaccc tctctccaag gccctctcct ggtctccctt cttctagaac cccttcctcc 241 acctccctct ctgcagaact tctcctttac cccccacccc ccaccactgc cccctttcct 301 tttctgacct ccttttggag ggctcagcgc tgcccagacc ataggagaga tgtgggaggc 361 tcagttcctg ggcttgctgt ttctgcagcc gctttgggtg gctccagtga agcctctcca 421 gccaggggct gaggtcccgg tggtgtgggc ccaggagggg gctcctgccc agctcccctg 481 cagccccaca atccccctcc aggatctcag ccttctgcga agagcagggg tcacttggca 541 gcatcagcca gacagtggcc cgcccgctgc cgcccccggc catcccctgg cccccggccc 601 tcacccggcg gcgccctcct cctgggggcc caggccccgc cgctacacgg tgctgagcgt 661 gggtcccgga ggcctgcgca gcgggaggct gcccctgcag ccccgcgtcc agctggatga 721 gcgcggccgg cagcgcgggg acttctcgct atggctgcgc ccagcccggc gcgcggacgc 781 cggcgagtac cgcgccgcgg tgcacctcag ggaccgcgcc ctctcctgcc gcctccgtct 841 gcgcctgggc caggcctcga tgactgccag ccccccagga tctctcagag cctccgactg 901 ggtcattttg aactgctcct tcagccgccc tgaccgccca gcctctgtgc attggttccg 961 gaaccggggc cagggccgag tccctgtccg ggagtccccc catcaccact tagcggaaag 1021 cttcctcttc ctgccccaag tcagccccat ggactctggg ccctggggct gcatcctcac 1081 ctacagagat ggcttcaacg tctccatcat gtataacctc actgttctgg gtctggagcc 1141 cccaactccc ttgacagtgt acgctggagc aggttccagg gtggggctgc cctgccgcct 1201 gcctgctggt gtggggaccc ggtctttcct cactgccaag tggactcctc ctgggggagg 1261 ccctgacctc ctggtgactg gagacaatgg cgactttacc cttcgactag aggatgtgag 1321 ccaggcccag gctgggacct acacctgcca tatccatctg caggaacagc agctcaatgc 1381 cactgtcaca ttggcaatca tcacagtgac tcccaaatcc tttgggtcac ctggatccct 1441 ggggaagctg ctttgtgagg tgactccagt atctggacaa gaacgctttg tgtggagctc 1501 tctggacacc ccatcccaga ggagtttctc aggaccttgg ctggaggcac aggaggccca 1561 gctcctttcc cagccttggc aatgccagct gtaccagggg gagaggcttc ttggagcagc 1621 agtgtacttc acagagctgt ctagcccagg tgcccaacgc tctgggagag ccccaggtgc 1681 cctcccagca ggccacctcc tgctgtttct catccttggt gtcctttctc tgctcctttt 1741 ggtgactgga gcctttggct ttcacctttg gagaagacag tggcgaccaa gacgattttc 1801 tgccttagag caagggattc accctccgca ggctcagagc aagatagagg agctggagca 1861 agaaccggag ccggagccgg agccggaacc ggagcccgag cccgagcccg agccggagca 1921 gctctgacct ggagctgagg cagccagcag atctcagcag cccagtccaa ataaactccc 1981 tgtcagcagc aaaaa

An exemplary human FCRL1 amino acid sequence is set forth below (SEQ ID NO: 134; GenBank Accession No: Q96LA6.1, Version 1, incorporated herein by reference):

1 mlprllllic aplcepaelf liaspshpte gspvtltckm pflqssdaqf qfcffrdtra 61 lgpgwssspk lqiaamwked tgsywceaqt maskvlrsrr sqinvhrvpv advsletqpp 121 ggqvmegdrl vlicsvamgt gditflwykg avglnlqskt qrsltaeyei psvresdaeq 181 yycvaengyg pspsglvsit vripvsrpil mlrapraqaa vedvlelhce alrgsppily 241 wfyheditlg srsapsggga sfnlslteeh sgnysceann glgaqrseav tlnftvptga 301 rsnhltsgvi egllstlgpa tvallfcygl krkigrrsar dplrslpspl pqeftylnsp 361 tpgqlqpiye nvnvvsgdev yslayynqpe qesvaaetlg thmedkvsld iysrlrkani 421 tdvdyedam

An exemplary human FCRL1 nucleic acid sequence is set forth below (SEQ ID NO: 135; GenBank Accession No: NM_052938.4, Version 4, incorporated herein by reference):

1 aacttccgat atcaacttcc tcaaacctct gatgagctgc tgctgctcga ctctgaggtg 61 cattcttttt ttgatgagag gcatctctag gtaccatccc tgacctggtc ctcatgctgc 121 cgaggctgtt gctgttgatc tgtgctccac tctgtgaacc tgccgagctg tttttgatag 181 ccagcccctc ccatcccaca gaggggagcc cagtgaccct gacgtgtaag atgccctttc 241 tacagagttc agatgcccag ttccagttct gctttttcag agacacccgg gccttgggcc 301 caggctggag cagctccccc aagctccaga tcgctgccat gtggaaagaa gacacagggt 361 catactggtg cgaggcacag acaatggcgt ccaaagtctt gaggagcagg agatcccaga 421 taaatgtgca cagggtccct gtcgctgatg tgagcttgga gactcagccc ccaggaggac 481 aggtgatgga gggagacagg ctggtcctca tctgctcagt tgctatgggc acaggagaca 541 tcaccttcct ttggtacaaa ggggctgtag gtttaaacct tcagtcaaag acccagcgtt 601 cactgacagc agagtatgag attccttcag tgagggagag tgatgctgag caatattact 661 gtgtagctga aaatggctat ggtcccagcc ccagtgggct ggtgagcatc actgtcagaa 721 tcccggtgtc tcgcccaatc ctcatgctca gggctcccag ggcccaggct gcagtggagg 781 atgtgctgga gcttcactgt gaggccctga gaggctctcc tccgatcctg tactggtttt 841 atcacgagga tatcaccctg gggagcaggt cggccccctc tggaggagga gcctccttca 901 acctttccct gactgaagaa cattctggaa actactcctg tgaggccaac aatggcctgg 961 gggcccagcg cagtgaggcg gtgacactca acttcacagt gcctactggg gccagaagca 1021 atcatcttac ctcaggagtc attgaggggc tgctcagcac ccttggtcca gccaccgtgg 1081 ccttattatt ttgctacggc ctcaaaagaa aaataggaag acgttcagcc agggatccac 1141 tcaggagcct tcccagccct ctaccccaag agttcaccta cctcaactca cctaccccag 1201 ggcagctaca gcctatatat gaaaatgtga atgttgtaag tggggatgag gtttattcac 1261 tggcgtacta taaccagccg gagcaggaat cagtagcagc agaaaccctg gggacacata 1321 tggaggacaa ggtttcctta gacatctatt ccaggctgag gaaagcaaac attacagatg 1381 tggactatga agatgctatg taaggttatg gaagattctg ctctttgaaa accatccatg 1441 accccaagcc tcaggcctga tatgttcttc agagatcctg gggcattagc tttccagtat 1501 acctcttctg gatgccattc tccatggcac tattccttca tctactgtga agtgaagttg 1561 gcgcagccct gaagaaacta cctaggagaa ctaatagaca caggagtgac agggactttg 1621 ttatcagaac cagattcctg ccggctcctt tgaaaacagg tcatattgtg ctcttctgtt 1681 tacaagagga aacaagatgg aataaaagaa attgggatct tgggttggag ggacagtgaa 1741 gcttagagca catgaactca aggttagtga ctctgcagga cttcacagag agagctgtgc 1801 ccatcattca gtccaagtgc tttctctgcc cagacagcac agaactccag ccccgctact 1861 tacatggatc atcgagtttc cacctaaaat atgattctat ttattttgag tcactgttac 1921 caaattagaa ctaaaacaaa gttacataaa aagttattgt gactccactt aattttagtg 1981 acgtattttt gtatatatag gccaacctat accacatcca aaattatgta tctattacag 2041 cccctagaag ctttataaat acagtgtgtc ttcttttatt cacaaaattt ttgaaatcgt 2101 ggtaatatgg tttgaaacct gtatcttaat tatttttttt ttaaattgag acagggtctc 2161 actctgtcac tcaatctgga atgcagtggc acaatcttgc ctcactgcaa cgcctgcctc 2221 tcaggctcaa gcaaacctct cacctcagcc tgctgagtag ctgggactac aggcacatgc 2281 caccaaactt ggccattttt tgtcttacgt agagacaaga tttcaccgtt ttgcccaggc 2341 tggtctcaaa ctcctgggct caagcaatgt attgaatttt aaaataacca ggcactcact 2401 cttatgaatt aataaacatt tggaggtata taaagtaaaa agttaaagtc tttcctgtaa 2461 gttaacacaa atgttaacta ttgttaaaaa ctttacaggt agctctctag atatttttct 2521 atttttgtat gtatacttat gcatacatgt aagtatataa acatttagaa gtgtacctat 2581 ctaacaaact attatgaaat actttcaaat ctgtaaatag atctattata ctattttaaa 2641 agtctctata gtagtgtgtt atatagataa atcataactt ttttcttttt ttattgtagt 2701 aaatatgcac aacataaaat tgatcatttt aaccattttt aagtgtacaa ttcagtggca 2761 ttaagtacta tcataatata ttttaatcct tctcatcact ggtggacatt aaggagactc 2821 tcaaaaaatt catattataa aaacaaagtt caaacaaatg tctttgtact agcatattat 2881 ggcactcctg ctggattatc tgaaggataa atttgtaaat ctagtattgc tagattatgc 2941 atattaaata ttcttgttaa atagtcttca atgtctctca ggtaaggctg tatcaattta 3001 tatcttcacc aacaacgtct gggaaatcag tttgtggggt gtattactta gttttcacat 3061 tgctaataaa gacatatcca agactgggta atttataaaa aaaaaaaaaa aaaaaa

An exemplary human FCRL3 amino acid sequence is set forth below (SEQ ID NO: 136; GenBank Accession No: AAH28933.1, Version 1, incorporated herein by reference):

1 mllwllllil tpgreqsgva pkavlllnpp wstafkgekv alicssishs laqgdtywyh 61 dekllkikhd kiqitepgny qcktrgssls davhvefspd wlilqalhpv fegdnvilrc 121 qgkdnknthq kvyykdgkql pnsynlekit vnsysrdnsk yhctayrkfy ildievtskp 181 lniqvqelfl hpvlrassst piegspmtlt cetqlspqrp dvqlqfslfr dsqtlglgws 241 rsprlqipam wtedsgsywc evetvthsik krslrsqirv qrvpvsnvnl eirptggqli 301 egenmvlics vaqgsgtvtf swhkegrvrs lgrktqrsll aelhvltvke sdagryycaa 361 dnvhspilst wirvtvripv shpvltfrap rahtvvgdll elhceslrgs ppilyrfyhe 421 dvtlgnssap sgggasfnls ltaehsgnys cdadnglgaq hshgvslrvt vpvsrpvltl 481 rapgaqavvg dllelhcesl rgsfpilywf yheddtlgni sahsgggasf nlslttehsg 541 nysceadngl gaqhskvvtl nvtgtsrnrt gltaagitgl vlsilvlaaa aallhyarar 601 rkpgglsatg tsshspsecq epsssrpsri dpqepthskp lapmelepmy snvnpgdsnp 661 iysqiwsiqh tkensancpm mhqeheeltv lyselkkthp ddsageassr graheeddee 721 nyenilnprk nkvqdfpcic nt

An exemplary human FCRL3 nucleic acid sequence is set forth below (SEQ ID NO: 137; GenBank Accession No: NM_052939.3, Version 3, incorporated herein by reference):

1 agtgaagggg tttcccatat gaaaaataca gaaagaatta tttgaatact agcaaataca 61 caacttgata tttctagaga acccaggcac agtcttggag acattactcc tgagagactg 121 cagctgatgg aagatgagcc ccaacttcta aaaatgtatc actaccggga ttgagataca 181 aacagcattt aggaaggtct catctgagta gcagcttcct gccctccttc ttggagataa 241 gtcgggcttt tggtgagaca gactttccca accctctgcc cggccggtgc ccatgcttct 301 gtggctgctg ctgctgatcc tgactcctgg aagagaacaa tcaggggtgg ccccaaaagc 361 tgtacttctc ctcaatcctc catggtccac agccttcaaa ggagaaaaag tggctctcat 421 atgcagcagc atatcacatt ccctagccca gggagacaca tattggtatc acgatgagaa 481 gttgttgaaa ataaaacatg acaagatcca aattacagag cctggaaatt accaatgtaa 541 gacccgagga tcctccctca gtgatgccgt gcatgtggaa ttttcacctg actggctgat 601 cctgcaggct ttacatcctg tctttgaagg agacaatgtc attctgagat gtcaggggaa 661 agacaacaaa aacactcatc aaaaggttta ctacaaggat ggaaaacagc ttcctaatag 721 ttataattta gagaagatca cagtgaattc agtctccagg gataatagca aatatcattg 781 tactgcttat aggaagtttt acatacttga cattgaagta acttcaaaac ccctaaatat 841 ccaagttcaa gagctgtttc tacatcctgt gctgagagcc agctcttcca cgcccataga 901 ggggagtccc atgaccctga cctgtgagac ccagctctct ccacagaggc cagatgtcca 961 gctgcaattc tccctcttca gagatagcca gaccctcgga ttgggctgga gcaggtcccc 1021 cagactccag atccctgcca tgtggactga agactcaggg tcttactggt gtgaggtgga 1081 gacagtgact cacagcatca aaaaaaggag cctgagatct cagatacgtg tacagagagt 1141 ccctgtgtct aatgtgaatc tagagatccg gcccaccgga gggcagctga ttgaaggaga 1201 aaatatggtc cttatttgct cagtagccca gggttcaggg actgtcacat tctcctggca 1261 caaagaagga agagtaagaa gcctgggtag aaagacccag cgttccctgt tggcagagct 1321 gcatgttctc accgtgaagg agagtgatgc agggagatac tactgtgcag ctgataacgt 1381 tcacagcccc atcctcagca cgtggattcg agtcaccgtg agaattccgg tatctcaccc 1441 tgtcctcacc ttcagggctc ccagggccca cactgtggtg ggggacctgc tggagcttca 1501 ctgtgagtcc ctgagaggct ctcccccgat cctgtaccga ttttatcatg aggatgtcac 1561 cctggggaac agctcagccc cctctggagg aggagcctcc ttcaacctct ctctgactgc 1621 agaacattct ggaaactact cctgtgatgc agacaatggc ctgggggccc agcacagtca 1681 tggagtgagt ctcagggtca cagttccggt gtctcgcccc gtcctcaccc tcagggctcc 1741 cggggcccag gctgtggtgg gggacctgct ggagcttcac tgtgagtccc tgagaggctc 1801 cttcccgatc ctgtactggt tttatcacga ggatgacacc ttggggaaca tctcggccca 1861 ctctggagga ggggcatcct tcaacctctc tctgactaca gaacattctg gaaactactc 1921 atgtgaggct gacaatggcc tgggggccca gcacagtaaa gtggtgacac tcaatgttac 1981 aggaacttcc aggaacagaa caggccttac cgctgcggga atcacggggc tggtgctcag 2041 catcctcgtc cttgctgctg ctgctgctct gctgcattac gccagggccc gaaggaaacc 2101 aggaggactt tctgccactg gaacatctag tcacagtcct agtgagtgtc aggagccttc 2161 ctcgtccagg ccttccagga tagaccctca agagcccact cactctaaac cactagcccc 2221 aatggagctg gagccaatgt acagcaatgt aaatcctgga gatagcaacc cgatttattc 2281 ccagatctgg agcatccagc atacaaaaga aaactcagct aattgtccaa tgatgcatca 2341 agagcatgag gaacttacag tcctctattc agaactgaag aagacacacc cagacgactc 2401 tgcaggggag gctagcagca gaggcagggc ccatgaagaa gatgatgaag aaaactatga 2461 gaatgtacca cgtgtattac tggcctcaga ccactagccc cttacccaga gtggcccaca 2521 ggaaacagcc tgcaccattt ttttttctgt tctctccaac cacacatcat ccatctctcc 2581 agactctgcc tcctacgagg ctgggctgca gggtatgtga ggctgagcaa aaggtctgca 2641 aatctcccct gtgcctgatc tgtgtgttcc ccaggaagag agcaggcagc ctctgagcaa 2701 gcactgtgtt attttcacag tggagacacg tggcaaggca ggagggccct cagctcctag 2761 ggctgtcgaa tagaggagga gagagaaatg gtctagccag ggttacaagg gcacaatcat 2821 gaccatttga tccaagtgtg atcgaaagct gttaatgtgc tctctgtata aacaatttgc 2881 tccaaatatt ttgtttccct tttttgtgtg gctggtagtg gcattgctga tgttttggtg 2941 tatatgctgt atccttgcta ccatattggg aacagccaaa agaagttata gaacaagaat 3001 ttaaggtgac tctatctga

An exemplary human SIGLEC8 amino acid sequence is set forth below (SEQ ID NO: 138; GenBank Accession No: Q9NYZ4.2, Version 2, incorporated herein by reference):

1 mlllllllpl lwgtkgmegd rqygdgyllq vqelvtvqeg lcvhvpcsfs ypqdgwtdsd 61 pvhgywfrag drpyqdapva tnnpdrevqa etqgrfqllg diwsndcsls irdarkrdkg 121 syffrlergs mkwsyksqln yktkqlsvfv talthrpdil ilgtlesghs rnltcsvpwa 181 ckqgtppmis wigasvsspg pttarssvlt ltpkpqdhgt sltcqvtlpg tgvtttstvr 241 ldvsyppwnl tmtvfqgdat astalgngss lsvlegqslr lvcavnsnpp arlswtrgsl 301 tlcpsrssnp gllelprvhv rdegeftcra qnaqgsqhis lslslqnegt gtsrpvsqvt 361 laavggagat alaflsfcii fiivrscrkk sarpaagvgd tgmedakair gsasqgplte 421 swkdgnplkk pppavapssg eegelhyatl sfhkvkpqdp qgqeatdsey seikihkret 481 aetqaclrnh npsskevrg

An exemplary human SIGLEC8 nucleic acid sequence is set forth below (SEQ ID NO: 139; GenBank Accession No: NM_014442.2, Version 2, incorporated herein by reference):

1 agtttctgag agaagaaccc tgaggaacag acgttccctg gcggccctgg cgccttcaaa 61 cccagacatg ctgctgctgc tgctgctgct gcccctgctc tgggggacaa aggggatgga 121 gggagacaga caatatgggg atggttactt gctgcaagtg caggagctgg tgacggtgca 181 ggagggcctg tgtgtccatg tgccctgctc cttctcctac ccccaggatg gctggactga 241 ctctgaccca gttcatggct actggttccg ggcaggagac agaccatacc aagacgctcc 301 agtggccaca aacaacccag acagagaagt gcaggcagag acccagggcc gattccaact 361 ccttggggac atttggagca acgactgctc cctgagcatc agagacgcca ggaagaggga 421 taaggggtca tatttctttc ggctagagag aggaagcatg aaatggagtt acaaatcaca 481 gttgaattac aaaactaagc agctgtctgt gtttgtgaca gccctgaccc ataggcctga 541 catcctcatc ctagggaccc tagagtctgg ccactccagg aacctgacct gctctgtgcc 601 ctgggcctgt aagcagggga caccccccat gatctcctgg attggggcct ccgtgtcctc 661 cccgggcccc actactgccc gctcctcagt gctcaccctt accccaaagc cccaggacca 721 cggcaccagc ctcacctgtc aggtgacctt gcctgggaca ggtgtgacca cgaccagtac 781 cgtccgcctc gatgtgtcct accctccttg gaacttgacc atgactgtct tccaaggaga 841 tgccacagca tccacagccc tgggaaatgg ctcatctctt tcagtccttg agggccagtc 901 tctgcgcctg gtctgtgctg tcaacagcaa tccccctgcc aggctgagct ggacccgggg 961 gagcctgacc ctgtgcccct cacggtcctc aaaccctggg ctgctggagc tgcctcgagt 1021 gcacgtgagg gatgaagggg aattcacctg ccgagctcag aacgctcagg gctcccagca 1081 catttccctg agcctctccc tgcagaatga gggcacaggc acctcaagac ctgtatcaca 1141 agtgacactg gcagcagtcg ggggagctgg agccacagcc ctggccttcc tgtccttctg 1201 catcatcttc atcatagtga ggtcctgcag gaagaaatcg gcaaggccag cagcgggcgt 1261 gggggataca ggcatggaag atgcaaaggc catcaggggc tcggcctctc agggacccct 1321 gactgaatcc tggaaagatg gcaaccccct gaagaagcct cccccagctg ttgccccctc 1381 gtcaggggag gaaggagagc tccattatgc aaccctcagc ttccataaag tgaagcctca 1441 ggacccgcag ggacaggagg ccactgacag tgaatactcg gagatcaaga tccacaagcg 1501 agaaactgca gagactcagg cctgtttgag gaatcacaac ccctccagca aagaagtcag 1561 aggctgattc tcatagaaca agaaccctct agagccccat gctatgcagt aggtcaccag 1621 ggctccctcc tcctgtctaa ccaaaacttg gaccaatgtc tcccctttcc ccggctacca 1681 gggacccatc cctgcctcta gcttctacta cccaccattc tcctctcgac ctctctgagg 1741 ttgactattt tagattccac atagagatga ggtcatgtgg tacttgcctc tctgtgtgtg 1801 gctcatttta cacaaaaaaa tatcccctag gttcatccat gttctctcaa atgacagaat 1861 caagcactga atattttttt ttctttgaga gatggagttt cgctctgttg cccaggctgg 1921 agtgcagtgg ttcaatctct gctcactgca acctccacct cctgggttca aacgattctc 1981 ctgcctcagc ttcccaagta gctggtacta caggcgtgtg tcaccacgcc cagctaattt 2041 ttgtattttt tagtagagac ggggtttcac tataagtggg ccaggctagt ctcaaactcc 2101 tgacctcaag tgatctgcct gccttggcct cccaaagtgc tgggatttca ggcatgagcc 2161 accgcaccca gcttgcattg aatattttca aggagctaaa agaagatttt aaatggtctc 2221 acaaaaacag ataaatattt gcacagatgg gtgtgctaat cattgtgcct tgatggttcc 2281 acgatgtatc cgggtgtgga aatctcactg ggtctctctc aaggccactc ggctactcag 2341 gacagggctg gaatttaaag cctgtccgat tctgaggtct cttctctcat ctagcactga 2401 gtcaagcaat cagcaggctg ggcacccctt agccataagt tttcaggaaa taaattcctt 2461 gagggcattg acttttacaa aagagggagc agcaatggcc tagagtctca ggaacaagac 2521 aggtgcactg aggagatgaa ggccgggacc ccctgcccaa cctgtatggc gggtctgtac 2581 ttattttgtt tacccccaat ttaaaacgtt tttttttatt gcaggttgtt tgtttgatat 2641 ggtttggctg tgtccccacc caaatcttat ctagaattgt aatcagaatt ataatcccca 2701 tgtgttgggg gagggacctg gtgggaggtg ataggatcat gggggtggtt cccccatgct 2761 gttctgatag tgagtgagtt atcacgagat ctgatggttt tgtaagtggt ggtttcccct 2821 gctcttctct cttgcctgcc accatgtaag atgtgcctgg ttccccttcc gccatgattg 2881 taagtttcct gaggcctccc ccgccatgtg gaactgtgag tcaattacac ctctttcatt 2941 tataaattaa aaaaaaaaaa aaaaaaa

An exemplary human FAIM3/TOSO amino acid sequence is set forth below (SEQ ID NO: 140; GenBank Accession No: 060667.1, Version 1, incorporated herein by reference):

1 mdfwlwplyf lpvsgalril pevkvegelg gsvtikcplp emhvriylcr emagsgtcgt 61 vvsttnfika eykgrvtlkq yprknlflve vtqltesdsg vyacgagmnt drgktqkvtl 121 nvhseyepsw eeqpmpetpk wfhlpylfqm payassskfv trvttpaqrg kvppvhhssp 181 ttqithrprv srassvagdk prtflpstta skisalegll kpqtpsynhh trlhrqrald 241 ygsqsgregq gfhiliptil glfllallgl vvkraverrk alsrrarrla vrmralessq 301 rprgsprprs qnniysacpr rargadaagt geapvpgpga plppaplqvs espwlhapsl 361 ktsceyvsly hqpaammeds dsddyinvpa

An exemplary human FAIM3/TOSO nucleic acid sequence is set forth below (SEQ ID NO: 141; GenBank Accession No: BC006401.2, Version 2, incorporated herein by reference):

1 atttcctcat cgtcaagctt tgttcctcgt gggggctaga aatctctttc cagttccaga 61 ttgtgaaggg ttcctgagta agcagcgtgt ctccatcccc ctctctaggg gctcttggat 121 ggaccttgca ctctagaagg gacaatggac ttctggcttt ggccacttta cttcctgcca 181 gtatcggggg ccctgaggat cctcccagaa gtaaaggtag agggggagct gggcggatca 241 gttaccatca agtgcccact tcctgaaatg catgtgagga tatatctgtg ccgggagatg 301 gctggatctg gaacatgtgg taccgtggta tccaccacca acttcatcaa ggcagaatac 361 aagggccgag ttactctgaa gcaataccca cgcaagaatc tgttcctagt ggaggtaaca 421 cagctgacag aaagtgacag cggagtctat gcctgcggag cgggcatgaa cacagaccgg 481 ggaaagaccc agaaagtcac cctgaatgtc cacagtgaat acgagccatc atgggaagag 541 cagccaatgc ctgagactcc aaaatggttt catctgccct atttgttcca gatgcctgca 601 tatgccagtt cttccaaatt cgtaaccaga gttaccacac cagctcaaag gggcaaggtc 661 cctccagttc accactcctc ccccaccacc caaatcaccc accgccctcg agtgtccaga 721 gcatcttcag tagcaggtga caagccccga accttcctgc catccactac agcctcaaaa 781 atctcagctc tggaggggct gctcaagccc cagacgccca gctacaacca ccacaccagg 841 ctgcacaggc agagagcact ggactatggc tcacagtctg ggagggaagg ccaaggattt 901 cacatcctga tcccgaccat cctgggcctt ttcctgctgg cacttctggg gctggtggtg 961 aaaagggccg ttgaaaggag gaaagccctc tccaggcggg cccgccgact ggccgtgagg 1021 atgcgcgccc tggagagctc ccagaggccc cgcgggtcgc cgcgaccgcg ctcccaaaac 1081 aacatctaca gcgcctgccc gcggcgcgct cgtggagcgg acgctgcagg cacaggggag 1141 gcccccgttc ccggccccgg agcgccgttg ccccccgccc cgctgcaggt gtctgaatct 1201 ccctggctcc atgccccatc tctgaagacc agctgtgaat acgtgagcct ctaccaccag 1261 cctgccgcca tgatggagga cagtgattca gatgactaca tcaatgttcc tgcctgacaa 1321 ctccccagct atcccccaac cccaggctcg gactgtggtg ccaaggagtc tcatctatct 1381 gctgatgtcc aatacctgct tcatgtgttc tcagagccct catcacttcc catgccccat 1441 ctcgactccc atccccatct atctgtgccc tgagcatggc tctgccccca ggtcgtcttg 1501 cacaccttgg cagccccctg tagttgacag gtaagctgta ggcatgtaga gcaattgtcc 1561 caatgccact tgcttccttt ccaagccgtc gaacagactg tgggatttgc agagtgtttc 1621 ttccatgtct ttgaccacag ggttgttgct gcccaggctc tagatcacat ggcatcaggc 1681 tggggcagag gcatagctat tgtctcgggc atccttccca gggttgggtc ttacacaaat 1741 agaaggctct tgctctgagt tatgtgacat gcctcagccc catggactaa gcaggggtct 1801 ggtataaaaa cactcctgga aacgcctttg ccctgatcca aatgttagca cttgctagtg 1861 aacgtctact tatctcaagt tctatgctaa aggcaattta tcttgatgtg atgataaacc 1921 aaacttatta gcaagatatg catatatatc aaaaaaaaaa aaaaaaaa

An exemplary human MAGEA2B amino acid sequence is set forth below (SEQ ID NO: 142; GenBank Accession No: AAI12161.1, Version 1, incorporated herein by reference):

1 mdfwlwplyf lpvsgalril pevkvegelg gsvtikcplp emhvriylcr emagsgtcgt 61 vvsttnfika eykgrvtlkq yprknlflve vtqltesdsg vyacgagmnt drgktqkvtl 121 nvhseyepsw eeqpmpetpk wfhlpylfqm payassskfv trvttpaqrg kvppvhhssp 181 ttqithrprv srassvagdk prtflpstta skisalegll kpqtpsynhh trlhrqrald 241 ygsqsgregq gfhiliptil glfllallgl vvkraverrk alsrrarrla vrmralessq 301 rprgsprprs qnniysacpr rargadaagt geapvpgpga plppaplqvs espwlhapsl 361 ktsceyvsly hqpaammeds dsddyinvpa

An exemplary human MAGEA2B nucleic acid sequence is set forth below (SEQ ID NO: 143; GenBank Accession No: NM_001321400.1, Version 1, incorporated herein by reference):

1 ttgcgcattg gaggtcagag gacagcgaga ttctcgccct gagcaacggc ctgacgtcgg 61 cggagggaag caggcgcagg ctccgtgagg aggcaagaat ccgggctttg cccctgcaat 121 caacccacgg aagctccggg aatggcggcc aagcacgcgg atcctgacgt tcacatatct 181 cagggagttg atgaccttgt tttcagaagg tgactcaggt caacacaggg gcccccatct 241 ggtcgacaga tgcagtggtt ctaggatctg ccaagcatcc aggtggagag cctgaggaat 301 caggagctcc aggaaccagg cagtgaggcc ttggtctgag tcagtgtcct caggtcacag 361 agcagagggg acgcagacag tgccaacact gaaggttctg agggggacag gctgacaagt 421 aggacccgag gcactggagg agcattgaag gagaagatct gcctgtgggt cttcattgcc 481 cagctcctgc ccgcactcct gcctgctgcc ctgaccagag tcatcatgcc tcttgagcag 541 aggagtcagc actgcaagcc tgaagaaggc cttgaggccc gaggagaggc cctgggcctg 601 gtgggtgcgc aggctcctgc tactgaggag cagcagaccg cttcttcctc ttctactcta 661 gtggaagtta ccctggggga ggtgcctgct gccgactcac cgagtcctcc ccacagtcct 721 cagggagcct ccagcttctc gactaccatc aactacactc tttggagaca atccgatgag 781 ggctccagca accaagaaga ggaggggcca agaatgtttc ccgacctgga gtccgagttc 841 caagcagcaa tcagtaggaa gatggttgag ttggttcatt ttctgctcct caagtatcga 901 gccagggagc cggtcacaaa ggcagaaatg ctggagagtg tcctcagaaa ttgccaggac 961 ttctttcccg tgatcttcag caaagcctcc gagtacttgc agctggtctt tggcatcgag 1021 gtggtggaag tggtccccat cagccacttg tacatccttg tcacctgcct gggcctctcc 1081 tacgatggcc tgctgggcga caatcaggtc atgcccaaga caggcctcct gataatcgtc 1141 ctggccataa tcgcaataga gggcgactgt gcccctgagg agaaaatctg ggaggagctg 1201 agtatgttgg aggtgtttga ggggagggag gacagtgtct tcgcacatcc caggaagctg 1261 ctcatgcaag atctggtgca ggaaaactac ctggagtacc ggcaggtgcc cggcagtgat 1321 cctgcatgct acgagttcct gtggggtcca agggccctca ttgaaaccag ctatgtgaaa 1381 gtcctgcacc atacactaaa gatcggtgga gaacctcaca tttcctaccc acccctgcat 1441 gaacgggctt tgagagaggg agaagagtga gtctcagcac atgttgcagc cagggccagt 1501 gggagggggt ctgggccagt gcaccttcca gggccccatc cattagcttc cactgcctcg 1561 tgtgatatga ggcccattcc tgcctctttg aagagagcag tcagcattct tagcagtgag 1621 tttctgttct gttggatgac tttgagattt atctttgttt cctgttggaa ttgttcaaat 1681 gttcctttta acaaatggtt ggatgaactt cagcatccaa gtttatgaat gacagtagtc 1741 acacatagtg ctgtttatat agtttagggg taagagtcct gttttttatt cagattggga 1801 aatccattcc attttgtgag ttgtcacata ataacagcag tggaatatgt atttgcctat 1861 attgtgaacg aattagcagt aaaatacatg atacaaggaa ctcaaaagat agttaattct 1921 tgccttatac ctcagtctat tatgtaaaat taaaaatatg tgtatgtttt tgcttctttg 1981 agaatgcaaa agaaattaaa tctgaataaa taattcttcc tgttca

An exemplary human MKRN9P amino acid sequence is set for the below (SEQ ID NO: 144; GenBank Accession No: Q6NVV0.1, Version 1, incorporated herein by reference):

1 mllaavgdde ltdsedesdl fheeledfyd ldl

An exemplary human MKRN9P nucleic acid sequence is set forth below (SEQ ID NO: 145; GenBank Accession No: NR_033410.1, Version 1, incorporated herein by reference):

1 gacgtggagc aggcagggac tgagcgggtg cctcagtgtc ctacccctcc cttcgccggg 61 cctctcagtc ctctcccagc agctggaccg gaactatgtg atcccggaag ttccggggcc 121 ttttctgtgt gggataaaca gtaatggcgg aggctgcagc tctcagacca acagccacaa 181 catcaggggc ggcagtggcg gcagcggcgg cggcggcagc agcggcctcc cctaccagga 241 tccccacagt caccattctg tccccagggg gcaggcgagg gggccgcggc agcgatggca 301 gcggcggcag ctggactaaa caggtcacct gcaggtattt tatgcatggg gtttataagg 361 aaggagataa ctgttgcaag ttgcatgacc tctctgacag tccgtataat gtagtgtaca 421 agagtttgca gccagggtac tgtatttatg gagactgctg cagatatgaa catagcaagc 481 cattgaaaca gaaagaagca actgctacag agctaactac aaagtcatcc cttgctgctt 541 cctcaagtct ctcatggata gtcggaccac ttgttgaaat gaatacgggt gaagctgagt 601 caagaaattc aaactttgta actgtaggag caggttcaga gggctgggtg aatgctgttg 661 agtttgttcc tgggcaaccc tactgtggcc gcactgcgcc ttcctgcact gaagcacccc 721 tgcagggctc agtgaccaag gaagaatcag agaaagagca aactgccgtg gaaacaaaga 781 agcagctgtg cccctatgct gcagtgggag agtgccgata tcgggagaac ttgtgtgtat 841 atggagattc gtgtgacatg tgtggctgca ggtcctgcat ctgatggatg ctgcccagag 901 atcacagcat ataaaatcat gctttgaggc ccatgagaaa gacagggagc tctcatttgc 961 tgtgcagcgc agcgaggaaa tggtgtgtga gagctgcatg gagatgatct atgagaaagc 1021 caaccccaga cagcaccgct tcgggatcct ctccaactgc aaccacacct actgtcttaa 1081 gtgcattcgc aagtggagga gtgctaagca gtttgagagc aagatcataa agtcctgccc 1141 agaatgtcgg atcacatcta actttgtcgt tccaagtgag tactgtgtgg aggagaaaga 1201 agagaagcag aaactcattc tgaaatacaa ggaggcaatg agcaacaagg cgtgcaggta 1261 ttttgatgaa ggacatggga gctgcccgtt tggagggaac ggtttttata agcatgtgta 1321 ccctgatggc cgtagagagg agccacagag acagaaggtg ggaacatcaa gcagataccc 1381 ggcccaatga aggaaccact tctgggaact cattgaggaa agagagaaca gcagcccctt 1441 tgacaacgat gaagaagagg ttgtcacctt tgagctgggt gagttgttgc ttatgctttt 1501 ggctgcagtt ggggacgatg aactaacaga ctctgaagat gagagcgact tgtttcatga 1561 ggagctggaa gatttttatg acttggatct atagcaacct tgtgtggcgt gtgaactggt 1621 ctgctgaccc cagacagcag ctgttccctg tggtggtgtg gcagtgcctg tgttctctcc 1681 taggcaggcc tgtcaactcc aggtgctggc ataagaattt ttacccaggg cctgtctttt 1741 caacccctca cctttcccca aggagtgtgt tgttttccct cttgaaaaaa agttagaaaa 1801 ataaatctta aagttagttt tctgaaa

An exemplary human MAGEC1 amino acid sequence is set forth below (SEQ ID NO: 146; GenBank Accession No: 060732.3, Version 3, incorporated herein by reference):

1 mgdkdmptag mpsllqssse spqscpeged sqsplqipqs spesddtlyp lqspqsrseg 61 edssdplqrp pegkdsqspl qipqsspegd dtqsplqnsq sspegkdsls pleisqsppe 121 gedvqsplqn passffssal lsifqsspes tqspfegfpq svlqipvsaa ssstlvsifq 181 sspestqspf egfpqsplqi pvsrsfsstl lsifqssper tqstfegfaq splqipvsps 241 ssstllslfq sfsertqstf egfaqsslqi pvspsfsstl vslfqssper tqstfegfpq 301 splqipvsss ssstllslfq ssperthstf egfpqsllqi pmtssfsstl lsifqsspes 361 aqstfegfpq splqipgsps fsstllslfq ssperthstf egfpqsplqi pmtssfsstl 421 lsilqsspes aqsafegfpq splqipvsss fsytllslfq ssperthstf egfpqsplqi 481 pvssssssst llslfqsspe ctqstfegfp qsplqipqsp pegenthspl qivpslpewe 541 dslsphyfpq sppqgedsls phyfpqsppq gedslsphyf pqspqgedsl sphyfpqspp 601 qgedsmsply fpqsplqgee fqsslqspvs icssstpssl pqsfpessqs ppegpvqspl 661 hspqsppegm hsqsplqspe sapegedsls plqipqsple gedslsslhf pqsppeweds 721 lsplhfpqfp pqgedfqssl qspvsicsss tslslpqsfp espqsppegp aqsplqrpvs 781 sffsytlasl lqsshespqs ppegpaqspl qspvssfpss tssslsqssp vssfpsstss 841 slsksspesp lqspvisfss stslspfsee ssspvdeyts ssdtllesds ltdseslies 901 eplftytlde kvdelarfll lkyqvkqpit kaemltnvis rytgyfpvif rkarefieil 961 fgislrevdp ddsyvfvntl dltsegclsd eqgmsqnrll ililsiifik gtyaseeviw 1021 dvlsgigvra grehfafgep relltkvwvq ehyleyrevp nssppryefl wgprahsevi 1081 krkvveflam lkntvpitfp ssykdalkdv eeraqaiidt tddstatesa sssvmspsfs 1141 se

An exemplary human MAGEC1 nucleic acid sequence is set forth below (SEQ ID NO: 147; GenBank Accession No: NM_005462.4, Version 4, incorporated herein by reference):

1 gctttgccgg atgtgctttc ccggcggcca tcttgggagt ctgaaggacc tgaggcattt 61 tgtgacgagg atcgtctcag gtcagcggag ggaggagact tatagaccta tccagtcttc 121 aaggtgctcc agaaagcagg agttgaagac ctgggtgtga gggacacata catcctaaaa 181 gcaccacagc agaggaggcc caggcagtgc caggagtcaa ggttcccaga agacaaaccc 241 cctaggaaga caggcgacct gtgaggccct agagcaccac cttaagagaa gaagagctgt 301 aagccggcct ttgtcagagc catcatgggg gacaaggata tgcctactgc tgggatgccg 361 agtcttctcc agagttcctc tgagagtcct cagagttgtc ctgaggggga ggactcccag 421 tctcctctcc agattcccca gagttctcct gagagcgacg acaccctgta tcctctccag 481 agtcctcaga gtcgttctga gggggaggac tcctcggatc ctctccagag acctcctgag 541 gggaaggact cccagtctcc tctccagatt ccccagagtt ctcctgaggg cgacgacacc 601 cagtctcctc tccagaattc tcagagttct cctgagggga aggactccct gtctcctcta 661 gagatttctc agagccctcc tgagggtgag gatgtccagt ctcctctgca gaatcctgcg 721 agttccttct tctcctctgc tttattgagt attttccaga gttcccctga gagtactcaa 781 agtccttttg agggttttcc ccagtctgtt ctccagattc ctgtgagcgc cgcctcctcc 841 tccactttag tgagtatttt ccagagttcc cctgagagta ctcaaagtcc ttttgagggt 901 tttccccagt ctccactcca gattcctgtg agccgctcct tctcctccac tttattgagt 961 attttccaga gttcccctga gagaactcag agtacttttg agggttttgc ccagtctcct 1021 ctccagattc ctgtgagccc ctcctcctcc tccactttac tgagtctttt ccagagtttc 1081 tctgagagaa ctcagagtac ttttgagggt tttgcccagt cttctctcca gattcctgtg 1141 agcccctcct tctcctccac tttagtgagt cttttccaga gttcccctga gagaactcag 1201 agtacttttg agggttttcc ccagtctcct ctccagattc ctgtgagctc ctcctcctcc 1261 tccactttat tgagtctttt ccagagttcc cctgagagaa ctcacagtac ttttgagggt 1321 tttccccagt ctcttctcca gattcctatg acctcctcct tctcctctac tttattgagt 1381 attttccaga gttctcctga gagtgctcaa agtacttttg agggttttcc ccagtctcct 1441 ctccagattc ctgggagccc ctccttctcc tccactttac tgagtctttt ccagagttcc 1501 cctgagagaa ctcacagtac ttttgagggt tttccccagt ctcctctcca gattcctatg 1561 acctcctcct tctcctctac tttattgagt attttacaga gttctcctga gagtgctcaa 1621 agtgcttttg agggttttcc ccagtctcct ctccagattc ctgtgagctc ctctttctcc 1681 tacactttat tgagtctttt ccagagttcc cctgagagaa ctcacagtac ttttgagggt 1741 tttccccagt ctcctctcca gattcctgtg agctcctcct cctcctcctc cactttattg 1801 agtcttttcc agagttcccc tgagtgtact caaagtactt ttgagggttt tccccagtct 1861 cctctccaga ttcctcagag tcctcctgaa ggggagaata cccattctcc tctccagatt 1921 gttccaagtc ttcctgagtg ggaggactcc ctgtctcctc actactttcc tcagagccct 1981 cctcaggggg aggactccct atctcctcac tactttcctc agagccctcc tcagggggag 2041 gactccctgt ctcctcacta ctttcctcag agccctcagg gggaggactc cctgtctcct 2101 cactactttc ctcagagccc tcctcagggg gaggactcca tgtctcctct ctactttcct 2161 cagagtcctc ttcaggggga ggaattccag tcttctctcc agagccctgt gagcatctgc 2221 tcctcctcca ctccatccag tcttccccag agtttccctg agagttctca gagtcctcct 2281 gaggggcctg tccagtctcc tctccatagt cctcagagcc ctcctgaggg gatgcactcc 2341 caatctcctc tccagagtcc tgagagtgct cctgaggggg aggattccct gtctcctctc 2401 caaattcctc agagtcctct tgagggagag gactccctgt cttctctcca ttttcctcag 2461 agtcctcctg agtgggagga ctccctctct cctctccact ttcctcagtt tcctcctcag 2521 ggggaggact tccagtcttc tctccagagt cctgtgagta tctgctcctc ctccacttct 2581 ttgagtcttc cccagagttt ccctgagagt cctcagagtc ctcctgaggg gcctgctcag 2641 tctcctctcc agagacctgt cagctccttc ttctcctaca ctttagcgag tcttctccaa 2701 agttcccatg agagtcctca gagtcctcct gaggggcctg cccagtctcc tctccagagt 2761 cctgtgagct ccttcccctc ctccacttca tcgagtcttt cccagagttc tcctgtgagc 2821 tccttcccct cctccacttc atcgagtctt tccaagagtt cccctgagag tcctctccag 2881 agtcctgtga tctccttctc ctcctccact tcattgagcc cattcagtga agagtccagc 2941 agcccagtag atgaatatac aagttcctca gacaccttgc tagagagtga ttccttgaca 3001 gacagcgagt ccttgataga gagcgagccc ttgttcactt atacactgga tgaaaaggtg 3061 gacgagttgg cgcggtttct tctcctcaaa tatcaagtga agcagcctat cacaaaggca 3121 gagatgctga cgaatgtcat cagcaggtac acgggctact ttcctgtgat cttcaggaaa 3181 gcccgtgagt tcatagagat actttttggc atttccctga gagaagtgga ccctgatgac 3241 tcctatgtct ttgtaaacac attagacctc acctctgagg ggtgtctgag tgatgagcag 3301 ggcatgtccc agaaccgcct cctgattctt attctgagta tcatcttcat aaagggcacc 3361 tatgcctctg aggaggtcat ctgggatgtg ctgagtggaa taggggtgcg tgctgggagg 3421 gagcactttg cctttgggga gcccagggag ctcctcacta aagtttgggt gcaggaacat 3481 tacctagagt accgggaggt gcccaactct tctcctcctc gttacgaatt cctgtggggt 3541 ccaagagctc attcagaagt cattaagagg aaagtagtag agtttttggc catgctaaag 3601 aataccgtcc ctattacctt tccatcctct tacaaggatg ctttgaaaga tgtggaagag 3661 agagcccagg ccataattga caccacagat gattcgactg ccacagaaag tgcaagctcc 3721 agtgtcatgt cccccagctt ctcttctgag tgaagtctag ggcagattct tccctctgag 3781 tttgaagggg gcagtcgagt ttctacgtgg tggagggcct ggttgaggct ggagagaaca 3841 cagtgctatt tgcatttctg ttccatatgg gtagttatgg ggtttacctg ttttactttt 3901 gggtattttt caaatgcttt tcctattaat aacaggttta aatagcttca gaatcctagt 3961 ttatgcacat gagtcgcaca tgtattgctg tttttctggt ttaagagtaa cagtttgata 4021 ttttgtaaaa acaaaaacac acccaaacac accacattgg gaaaaccttc tgcctcattt 4081 tgtgatgtgt cacaggttaa tgtggtgtta ctgtaggaat tttcttgaaa ctgtgaagga 4141 actctgcagt taaatagtgg aataaagtaa aggattgtta atgtttgcat ttcctcaggt 4201 cctttagtct gttgttcttg aaaactaaag atacatacct ggtttgcttg gcttacgtaa 4261 gaaagtagaa gaaagtaaac tgtaataaat aaaagtgtca gtgactcatt tatttgatga 4321 aaaaaaaaaa aaaaaaa

An exemplary human PSG11 amino acid sequence is set forth below (SEQ ID NO: 148; GenBank Accession No: AAA60203.1, Version 1, incorporated herein by reference):

1 mgpfpapsct qritwkglll tasllnfwnp pttaevtiea qppkvsegkd vlllvhnlpq 61 nlpgyfwykg emtdlyhyii syivdgkiii ygpaysgret vysnaslliq nvtrkdagty 121 tlhiikrgde treeirhftf tlyletpkpy isssnlnpre ameavrlicd petldasylw 181 wmngqslpvt hrlqlsktnr tlylfgvtky iagpyeceir npvsairsdp vtlnllpklp 241 ipyitinnln prenkdvlaf tcepksenyt yiwwlngqsl pvspgvkrpi enrililpsv 301 trnetgpyqc eirdrygglr snpvilnvly gpdlpriyps ftyyrsgenl dlscftesnp 361 paeyfwting kfqqsgqklf ipqitrnhsg lyacsvhnsa tgkeisksmt vkvsgpchgd 421 ltesqs

An exemplary human PSG11 nucleic acid sequence is set forth below (SEQ ID NO: 149; GenBank Accession No: M58591.1, Version 1, incorporated herein by reference):

1 cagccgtgct cagacagctt ctggatccta ggctcatctc cacagaggag aacacgcagg 61 cagcagagac catggggccc ttcccagccc cttcctgcac acagcgcatc acctggaagg 121 ggctcctgct cacagcatca cttttaaact tctggaaccc gcccaccact gccgaagtca 181 cgattgaagc ccagccaccc aaagtttctg aggggaagga tgttcttcta cttgtccaca 241 atttgcccca gaatcttcct ggctacttct ggtacaaagg ggaaatgacg gacctctacc 301 attacattat atcgtatata gttgatggta aaataattat atatgggcct gcatacagtg 361 gaagagaaac agtatattcc aacgcatccc tgctgatcca gaatgtcacc cggaaggatg 421 caggaaccta caccttacac atcataaagc gaggtgatga gactagagaa gaaattcgac 481 atttcacctt caccttatac ttggagactc ccaagcccta catctccagc agcaacttaa 541 accccaggga ggccatggag gctgtgcgct taatctgtga tcctgagact ctggacgcaa 601 gctacctatg gtggatgaat ggtcagagcc tccctgtgac tcacaggttg cagctgtcca 661 aaaccaacag gaccctctat ctatttggtg tcacaaagta tattgcagga ccctatgaat 721 gtgaaatacg gaacccagtg agtgccattc gcagtgaccc agtcaccctg aatctcctcc 781 cgaagctgcc catcccctac atcaccatca acaacttaaa ccccagggag aataaggatg 841 tcttagcctt cacctgtgaa cctaagagtg agaactacac ctacatttgg tggctaaacg 901 gtcagagcct ccccgtcagt cccggggtaa agcgacccat tgaaaacagg atactcattc 961 tacccagtgt cacgagaaat gaaacaggac cctatcaatg tgaaatacgg gaccgatatg 1021 gtggcctccg cagtaaccca gtcatcctaa atgtcctcta tggtccagac ctccccagaa 1081 tttacccttc attcacctat taccgttcag gagaaaacct cgacttgtcc tgcttcacgg 1141 aatctaaccc accggcagag tatttttgga caattaatgg gaagtttcag caatcaggac 1201 aaaagctctt tatcccccaa attactagaa atcatagcgg gctctatgct tgctctgttc 1261 ataactcagc cactggcaag gaaatctcca aatccatgac agtcaaagtc tctggtccct 1321 gccatggaga cctgacagag tctcagtcat gactgcaaca actgagacac tgagaaaaag 1381 aacaggctga taccttcatg aaattcaaga caaagaagaa aaaaactcaa tgttattgga 1441 ctaaataatc aaaaggataa tgttttcata attttttatt ggaaaatgtg ctgattcttt 1501 gaatgtttta ttctccagat ttatgaactt tttttcttca gcaattggta aagtatactt 1561 ttgtaaacaa aaattgaaat atttgctttt gctgtctatc tgaatgcccc agaattgtga 1621 aactattcat gagtattcat aggtttatgg taataaagtt atttgcacat gttccgta

An exemplary human TAC3 amino acid sequence is set forth below (SEQ ID NO: 150; GenBank Accession No: AAQ89042.1, Version 1, incorporated herein by reference):

1 mrimllftai lafslaqsfg avckepqeev vpgggrskrd pdlyqllqrl fkshsslegl 61 lkalsqastd pkestspekr dmhdffvglm gkrsvqpegk tgpflpsvrv prplhpnqlg 121 stgksslgte eqrpl

An exemplary human TAC3 nucleic acid sequence is set forth below (SEQ ID NO: 151; GenBank Accession No: AY358679.1, Version 1, incorporated herein by reference):

1 agtgactgca gccttcctag atcccctcca ctcggtttct ctctttgcag gagcaccggc 61 agcaccagtg tgtgagggga gcaggcagcg gtcctagcca gttccttgat cctgccagac 121 cacccagccc ccggcacaga gctgctccac aggcaccatg aggatcatgc tgctattcac 181 agccatcctg gccttcagcc tagctcagag ctttggggct gtctgtaagg agccacagga 241 ggaggtggtt cctggcgggg gccgcagcaa gagggatcca gatctctacc agctgctcca 301 gagactcttc aaaagccact catctctgga gggattgctc aaagccctga gccaggctag 361 cacagatcct aaggaatcaa catctcccga gaaacgtgac atgcatgact tctttgtggg 421 acttatgggc aagaggagcg tccagccaga gggaaagaca ggacctttct taccttcagt 481 gagggttcct cggccccttc atcccaatca gcttggatcc acaggaaagt cttccctggg 541 aacagaggag cagagacctt tataagactc tcctacggat gtgaatcaag agaacgtccc 601 cagctttggc atcctcaagt atcccccgag agcagaatag gtactccact tccggactcc 661 tggactgcat taggaagacc tctttccctg tcccaatccc caggtgcgca cgctcctgtt 721 accctttctc ttccctgttc ttgtaacatt cttgtgcttt gactccttct ccatcttttc 781 tacctgaccc tggtgtggaa actgcatagt gaatatcccc aaccccaatg ggcattgact 841 gtagaatacc ctagagttcc tgtagtgtcc tacattaaaa atataatgtc tctctctatt 901 cctcaacaat aaaggatttt tgcatatgaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 961 aaaaaaaaaa aa

An exemplary human PSG8 amino acid sequence is set forth below (SEQ ID NO: 152; GenBank Accession No: Q9UQ74.2, Version 2, incorporated herein by reference):

1 mgllsappct qritwkglll tasllnfwnp pttaqvtiea qptkvsegkd vlllvhnlpq 61 nitgyiwykg qirdlyhyit syvvdgqiii ygpaysgret iysnaslliq nvtqedagsy 121 tlhiimggde nrgvtghftf tlyletpkps isssklnpre ameaysltcd petpdasylw 181 wmngqslpms hrlqlsetnr tlfllgvtky tagpyeceir npvsasrsdp ftlnllpklp 241 kpyitinnlk prenkdvlnf tcepksenyt yiwwlngqsl pvsprvkrpi enrililpsv 301 trnetgpyqc eirdqyggir sypvtlnvly gpdlpriyps ftyyrsgevl ylscsadsnp 361 paqyswting kfqlsgqklf ipqittkhsg lyacsvrnsa tgkessksmt vkvsgkripv 421 slaigi

An exemplary human PSG8 nucleic acid sequence is set forth below (SEQ ID NO: 153; GenBank Accession No: AH007519.2, Version 2, incorporated herein by reference):

    1 aggactctgc ttgcccaacc tgcagggtat gtttctgact gtgtaggtct gtgtgtgtcc    61 ttctgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt   121 ctgcacaaag tgtgtgttga ggtttggtga aagaatcact gctgaaaaaa ggcagaggcc   181 tccacaattc ccagggacct gaaacacaga caaaaggaaa aacaggaggg acaaggaggc   241 aggactgaga gaggagggga cagagaggtg tcctgggcct gaccccgccc atgaacctga   301 gaggtgctcc tgccccggga agaagctcag cgcagaagga ggcaggacag cactgctgag   361 agctgtgctc aggaagcttc tggatcctag gctcatctcc acagaggaga acacacagac   421 agcagagacc atggggctcc tctcagcccc tccctgcaca cagcgcatca cctggaaggg   481 gctcctgctc acaggtgagg agagaacctc ctgggagagg acaggaggag gaagcagagt   541 gactggatgg ggtctccttg agagtatggg gtactaaaaa atgaaagaag ccagcacttt   601 gggaggctga ggcaggtgga tcatgagatc aggagttcaa gatcagtctg gccaacacag   661 tgaagccctg tctctactaa aaatacaaaa atttaaccag atattgtggt gtgctcctct   721 aatcctagct actcgggagg ctgaggcaga agaatcacgt gaacccagga ggcagaagtt   781 gcagctagct gagatagtgc catcgcacgc cagcctggga gacagtatga gactccatct   841 caaaaaaaaa aaaagagaaa aaagagaaaa aggaaagaag gctctattgg agcctggata   901 gggggaaata caccagagag ggacaggggt caaaacagga aagtcacagg aaccagaatt   961 ggtaagaggt aggaaaatct tgtgttctgt tttcctgatt aatcatcagg ggccaccaca  1021 ttttgaatat gataataata actgtatcag atgacacttc acataaaann nnnnnnnnnn  1081 nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn  1141 nnnnnnnnnn nnnnnnnnnn nnnnnnnnaa aaatgccaag gtcagaagtg ttgaaggaat  1201 gggggtcatg gggctgacct tgacctagta ggatagtagg acacacacac atacacacac  1261 acagacacac atgccgcttt tgtgtgtgtg tgtgcgtgtg tttgtatgtg tgtgtgtctg  1321 tgtcttcaag gctgaggact gaagagaact tctcaggacc cagggcccca tgttttcaca  1381 ccaatacata gctctcaata ttgactgatg ctctctccac ctcctagcat cacttttaaa  1441 cttctggaac ccacccacga ctgcccaagt cacgattgaa gcccagccaa ccaaagtttc  1501 tgaggggaag gatgttcttc tacttgtcca caatttgccc cagaatctta ctggctacat  1561 ctggtacaaa gggcaaatca gggacctcta ccattacatt acatcatatg tagtagacgg  1621 tcaaataatt atatatgggc ctgcatacag tggacgagaa acaatatatt ccaatgcatc  1681 cctgctgatc cagaatgtca cccaggaaga cgcaggatcc tacaccttac acatcataat  1741 gggaggtgat gagaatagag gagtaactgg acatttcacc ttcaccttat atcgtgagtg  1801 attccacatg atccctgggt gttgggggac aggggtcact tctacttcac acacacagga  1861 ttgtcaggcc tggacattgc ctgtgtccct ctctgcatta tgtcccatgc tggggtttgg  1921 gcatttagtg caggacacac acagaggaga caaatttcaa cagatcagaa ttc

An exemplary human HSPB3 amino acid sequence is set forth below (SEQ ID NO: 154; GenBank Accession No: Q12988.2, Version 2, incorporated herein by reference):

    1 makiilrhli eipvryqeef eargledcrl dhalyalpgp tivdlrktra aqsppvdsaa    61 etppregksh fqilldvvqf lpediiiqtf egwllikaqh gtrmdehgfi srsftrqykl   121 pdgveikdls avlchdgilv vevkdpvgtk

An exemplary human HSPB3 nucleic acid sequence is set forth below (SEQ ID NO: 155; GenBank Accession No: CR450314.1, Version 1, incorporated herein by reference):

    1 atggcaaaaa tcattttgag gcacctcata gagattccag tgcgttacca ggaagagttt    61 gaagctcgag gtctagaaga ctgcaggctg gatcatgctt tatatgcact gcctgggcca   121 accatcgtgg acctgaggaa aaccagggca gcgcagtctc ctccagtgga ctcagcggca   181 gagacgccac cccgagaagg caaatcccac tttcagatcc tgctggacgt ggtccagttc   241 ctccctgaag acatcatcat tcagaccttc gaaggctggc tgctgataaa agcacaacac   301 ggaaccagaa tggatgagca cggttttatc tcaagaagct tcacccgaca gtacaaacta   361 ccagatggtg tggaaatcaa agatttgtct gcagtcctct gtcatgatgg aattttggtg   421 gtggaagtaa aggatccagt tgggactaag

An exemplary human GJB6 amino acid sequence is set forth below (SEQ ID NO: 156; GenBank Accession No: 095452.2, Version 2, incorporated herein by reference):

    1 mdwgtlhtfi ggvnkhstsi gkvwitvifi frvmilvvaa qevwgdeqed fvcntlqpgc    61 knvcydhffp vshirlwalq lifvstpall vamhvayyrh ettrkfrrge krndfkdied   121 ikkqkvrieg slwwtytssi ffriifeaaf myvfyflyng yhlpwvlkcg idpcpnlvdc   181 fisrptektv ftifmisasv icmllnvael cylllkvcfr rskraqtqkn hpnhalkesk   241 qnemnelisd sgqnaitgfp s

An exemplary human GJB6 nucleic acid sequence is set forth below (SEQ ID NO: 157; GenBank Accession No: AY297110.1, Version 1, incorporated herein by reference):

    1 atggattggg ggacgctgca cactttcatc gggggtgtca acaaacactc caccagcatc    61 gggaaggtgt ggatcacagt catctttatt ttccgagtca tgatcctcgt ggtggctgcc   121 caggaagtgt ggggtgacga gcaagaggac ttcgtctgca acacactgca accgggatgc   181 aaaaatgtgt gctatgacca ctttttcccg gtgtcccaca tccggctgtg ggccctccag   241 ctgatcttcg tctccacccc agcgctgctg gtggccatgc atgtggccta ctacaggcac   301 gaaaccactc gcaagttcag gcgaggagag aagaggaatg atttcaaaga catagaggac   361 attaaaaagc agaaggttcg gatagagggg tcgctgtggt ggacgtacac cagcagcatc   421 tttttccgaa tcatctttga agcagccttt atgtatgtgt tttacttcct ttacaatggg   481 taccacctgc cctgggtgtt gaaatgtggg attgacccct gccccaacct tgttgactgc   541 tttatttcta ggccaacaga gaagaccgtg tttaccattt ttatgatttc tgcgtctgtg   601 atttgcatgc tgcttaacgt ggcagagttg tgctacctgc tgctgaaagt gtgttttagg   661 agatcaaaga gagcacagac gcaaaaaaat caccccaatc atgccctaaa ggagagtaag   721 cagaatgaaa tgaatgagct gatttcagat agtggtcaaa atgcaatcac aggtttccca   781 agctaa

An exemplary human MAGEA1 amino acid sequence is set forth below (SEQ ID NO: 158; GenBank Accession No: P43355.1, Version 1, incorporated herein by reference):

    1 msleqrslhc kpeealeaqq ealglvcvqa atssssplvl gtleevptag stdppqspqg    61 asafpttinf trqrqpsegs ssreeegpst scileslfra vitkkvadlv gflllkyrar   121 epvtkaemle sviknykhcf peifgkases lqlvfgidvk eadptghsyv lvtclglsyd   181 gllgdnqimp ktgfliivlv miamegghap eeeiweelsv mevydgrehs aygeprkllt   241 qdlvgekyle yrqvpdsdpa ryeflwgpra laetsyvkvl eyvikvsarv rfffpslrea   301 alreeeegv

An exemplary human MAGEA1 nucleic acid sequence is set forth below (SEQ ID NO: 159; GenBank Accession No: NM_004988.4, Version 4, incorporated herein by reference):

    1 agagagaagc gaggtttcca ttctgaggga cggcgtagag ttcggccgaa ggaacctgac    61 ccaggctctg tgaggaggca aggttttcag gggacaggcc aacccagagg acaggattcc   121 ctggaggcca cagaggagca ccaaggagaa gatctgcctg tgggtcttca ttgcccagct   181 cctgcccaca ctcctgcctg ctgccctgac gagagtcatc atgtctcttg agcagaggag   241 tctgcactgc aagcctgagg aagcccttga ggcccaacaa gaggccctgg gcctggtgtg   301 tgtgcaggct gccacctcct cctcctctcc tctggtcctg ggcaccctgg aggaggtgcc   361 cactgctggg tcaacagatc ctccccagag tcctcaggga gcctccgcct ttcccactac   421 catcaacttc actcgacaga ggcaacccag tgagggttcc agcagccgtg aagaggaggg   481 gccaagcacc tcttgtatcc tggagtcctt gttccgagca gtaatcacta agaaggtggc   541 tgatttggtt ggttttctgc tcctcaaata tcgagccagg gagccagtca caaaggcaga   601 aatgctggag agtgtcatca aaaattacaa gcactgtttt cctgagatct tcggcaaagc   661 ctctgagtcc ttgcagctgg tctttggcat tgacgtgaag gaagcagacc ccaccggcca   721 ctcctatgtc cttgtcacct gcctaggtct ctcctatgat ggcctgctgg gtgataatca   781 gatcatgccc aagacaggct tcctgataat tgtcctggtc atgattgcaa tggagggcgg   841 ccatgctcct gaggaggaaa tctgggagga gctgagtgtg atggaggtgt atgatgggag   901 ggagcacagt gcctatgggg agcccaggaa gctgctcacc caagatttgg tgcaggaaaa   961 gtacctggag taccggcagg tgccggacag tgatcccgca cgctatgagt tcctgtgggg  1021 tccaagggcc ctcgctgaaa ccagctatgt gaaagtcctt gagtatgtga tcaaggtcag  1081 tgcaagagtt cgctttttct tcccatccct gcgtgaagca gctttgagag aggaggaaga  1141 gggagtctga gcatgagttg cagccaaggc cagtgggagg gggactgggc cagtgcacct  1201 tccagggccg cgtccagcag cttcccctgc ctcgtgtgac atgaggccca ttcttcactc  1261 tgaagagagc ggtcagtgtt ctcagtagta ggtttctgtt ctattgggtg acttggagat  1321 ttatctttgt tctcttttgg aattgttcaa atgttttttt ttaagggatg gttgaatgaa  1381 cttcagcatc caagtttatg aatgacagca gtcacacagt tctgtgtata tagtttaagg  1441 gtaagagtct tgtgttttat tcagattggg aaatccattc tattttgtga attgggataa  1501 taacagcagt ggaataagta cttagaaatg tgaaaaatga gcagtaaaat agatgagata  1561 aagaactaaa gaaattaaga gatagtcaat tcttgcctta tacctcagtc tattctgtaa  1621 aatttttaaa gatatatgca tacctggatt tccttggctt ctttgagaat gtaagagaaa  1681 ttaaatctga ataaagaatt cttcctgtta aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa  1741 aaaaaaaaaa aaaaa

An exemplary human MAGEA11 amino acid sequence is set forth below (SEQ ID NO: 160; GenBank Accession No: P43364.2, Version 2, incorporated herein by reference):

    1 metqfrrggl gcspasikrk kkredsgdfg lqvstmfsed dfqsterapy gpqlqwsqdl    61 prvqvfreqa nledrsprrt qritggeqvl wgpitqifpt vrpadltrvi mpleqrsqhc   121 kpeeglqaqe edlglvgaqa lqaeeqeaaf fsstlnvgtl eelpaaesps ppqspqeesf   181 sptamdaifg slsdegsgsq ekegpstspd lidpesfsqd ilhdkiidlv hlllrkyrvk   241 glitkaemlg sviknyedyf peifreasvc mqllfgidvk evdptshsyv lvtslnlsyd   301 giqcneqsmp ksglliivlg vifmegncip eevmwevlsi mgvyagrehf lfgepkrllt   361 qnwvqekylv yrqvpgtdpa cyeflwgpra haetskmkvl eyianangrd ptsypslyed   421 alreegegv

An exemplary human MAGEA11 nucleic acid sequence is set forth below (SEQ ID NO: 161; GenBank Accession No: AY747607.1, Version 1, incorporated herein by reference):

    1 gagtggcaga gggcagcggg tccaggctcc atgaggaggc aagccttggg aatctgaggg    61 atggagactc agttccgcag agggggtctg gggtgcagcc ctgccagcat caagaggaag   121 aagaagaggg aggactcagg agactttgga ctccaggtga gcactatgtt ctcagaggac   181 gacttccagt caacagaaag agccccatat ggtccacaac tacagtggtc ccaggatctg   241 ccaagagtcc aggtttttag agaacaggcc aacctggagg acaggagtcc caggagaacc   301 cagaggatca ctggaggaga acaagtgctg tggggcccca tcacccagat atttcccaca   361 gttcggcctg ctgacctaac cagagtcatc atgcctcttg agcaaagaag tcagcactgc   421 aagcctgagg aaggccttca ggcccaagaa gaagacctgg gcctggtggg tgcacaggct   481 ctccaagctg aggagcagga ggctgccttc ttctcctcta ctctgaatgt gggcactcta   541 gaggagttgc ctgctgctga gtcaccaagt cctccccaga gtcctcagga agagtccttc   601 tctcccactg ccatggatgc catctttggg agcctatctg atgagggctc tggcagccaa   661 gaaaaggagg ggccaagtac ctcgcctgac ctgatagacc ctgagtcctt ttcccaagat   721 atactacatg acaagataat tgatttggtt catttattgc tccgcaagta tcgagtcaag   781 gggctgatca caaaggcaga aatgctgggg agtgtcatca aaaattatga ggactacttt   841 cctgagatat ttagggaagc ctctgtatgc atgcaactgc tctttggcat tgatgtgaag   901 gaagtggacc ccactagcca ctcctatgtc cttgtcacct ccctcaacct ctcttatgat   961 ggcatacagt gtaatgagca gagcatgccc aagtctggcc tcctgataat agtcctgggt  1021 gtaatcttca tggaggggaa ctgcatccct gaagaggtta tgtgggaagt cctgagcatt  1081 atgggggtgt atgctggaag ggagcacttc ctctttgggg agcccaagag gctccttacc  1141 caaaattggg tgcaggaaaa gtacctggtg taccggcagg tgcccggcac tgatcctgca  1201 tgctatgagt tcctgtgggg tccaagggcc cacgctgaga ccagcaagat gaaagttctt  1261 gagtacatag ccaatgccaa tgggagggat cccacttctt acccatccct gtatgaagat  1321 gctttgagag aggagggaga gggagtctga gcatgagatg caaccagggc cagcgggcag  1381 ggaaatgggc caatgcatgc ttcagggcca cacccagcag tttccctgtc ctgtgtgaaa  1441 tcaggcccat tcttccctct gtgtttgatg agagaagtca gtgttctcag tagtagaagg  1501 cacagtgaat ggaagggaac acattgtata ctgcctttag gtttctcttc catcgggtga  1561 cttggagatt tctttttgtt tccctttggt aattttcaaa tattgttcct gtaataaaag  1621 ttttagttag cttcaacatc taagtgtatg gatgatactg accacacatg ttgttttgct  1681 tatccatttc aagtgcaagt gtttgccatt ttgtaaaaca ttttgggaaa tcttccatct  1741 tgctgtgatt tgcaataggt attttcttgg agaatgtaag aacttaacaa taaagctgaa  1801 ctggtgttgt gaaacagaga aaaaaaaaaa aaaaaaa

An exemplary human MAGEA9B amino acid sequence is set forth below (SEQ ID NO: 162; GenBank Accession No: NP_001074259.1, Version 1, incorporated herein by reference):

    1 msleqrsphc kpdedleaqg edlglmgaqe ptgeeeetts ssdskeeevs aagsssppqs    61 pqggasssis vyytlwsqfd egsssqeeee psssvdpaql efmfqealkl kvaelvhfll   121 hkyrvkepvt kaemlesvik nykryfpvif gkasefmqvi fgtdvkevdp aghsyilvta   181 lglscdsmlg dghsmpkaal liivlgvilt kdncapeevi wealsvmgvy vgkehmfyge   241 prklltqdwv genyleyrqv pgsdpahyef lwgskahaet syekvinylv mlnarepicy   301 pslyeevlge eqegv

An exemplary human MAGEA9B nucleic acid sequence is set forth below (SEQ ID NO: 163; GenBank Accession No: NM_001080790.1, Version 1, incorporated herein by reference):

    1 gtgcgcactg ggggtcagag agaagggaga ggcctccttc tgaggggcgg cttgataccg    61 gtggaggagc tccaggaagc aggcaggcct tggtctgaga cagtgtcctc aggtcgcaga   121 gcagaggaga cccaggcagt gtcagcagtg aaggttctcg ggacaggcta accaggagga   181 caggagcccc aagaggcccc agagcagcac tgacgaagac ctgcctgtgg gtctccatcg   241 cccagctcct gcccacgctc ctgactgctg ccctgaccag agtcatcatg tctctcgagc   301 agaggagtcc gcactgcaag cctgatgaag accttgaagc ccaaggagag gacttgggcc   361 tgatgggtgc acaggaaccc acaggcgagg aggaggagac tacctcctcc tctgacagca   421 aggaggagga ggtgtctgct gctgggtcat caagtcctcc ccagagtcct cagggaggcg   481 cttcctcctc catttccgtc tactacactt tatggagcca attcgatgag ggctccagca   541 gtcaagaaga ggaagagcca agctcctcgg tcgacccagc tcagctggag ttcatgttcc   601 aagaagcact gaaattgaag gtggctgagt tggttcattt cctgctccac aaatatcgag   661 tcaaggagcc ggtcacaaag gcagaaatgc tggagagcgt catcaaaaat tacaagcgct   721 actttcctgt gatcttcggc aaagcctccg agttcatgca ggtgatcttt ggcactgatg   781 tgaaggaggt ggaccccgcc ggccactcct acatccttgt cactgctctt ggcctctcgt   841 gcgatagcat gctgggtgat ggtcatagca tgcccaaggc cgccctcctg atcattgtcc   901 tgggtgtgat cctaaccaaa gacaactgcg cccctgaaga ggttatctgg gaagcgttga   961 gtgtgatggg ggtgtatgtt gggaaggagc acatgttcta cggggagccc aggaagctgc  1021 tcacccaaga ttgggtgcag gaaaactacc tggagtaccg gcaggtgccc ggcagtgatc  1081 ctgcgcacta cgagttcctg tggggttcca aggcccacgc tgaaaccagc tatgagaagg  1141 tcataaatta tttggtcatg ctcaatgcaa gagagcccat ctgctaccca tccctttatg  1201 aagaggtttt gggagaggag caagagggag tctgagcacc agccgcagcc ggggccaaag  1261 tttgtggggt cagggcccca tccagcagct gccctgcccc atgtgacatg aggcccattc  1321 ttggctctgt gtttgaagag agcaatcagt gttctcagtg gcagtgggtg gaagtgagca  1381 cactgtatgt catctctggg ttccttgtct attgggtgat ttggagattt atccttgctc  1441 ccttttggaa ttgttcaaat gttcttttaa tggtcagttt aatgaacttc accatcgaag  1501 ttaatgaatg acagtagtca cacatattgc tgtttatgtt atttaggagt aagattcttg  1561 cttttgagtc acatggggaa atccctgtta ttttgtgaat tgggacaaga taacatagca  1621 gaggaattaa taattttttt gaaacttgaa cttagcagca aaatagagct cataaagaaa  1681 tagtgaaatg aaaatgtagt taattcttgc cttatacctc tttctctctc ctgtaaaatt  1741 aaaatatata catgtatacc tggatttgct tggcttcttt gagcatgtaa gagaaataaa  1801 aattgaaaga ataa

An exemplary human TRPM1 amino acid sequence is set forth below (SEQ ID NO: 164; GenBank Accession No: AAH58286.1, Version 1, incorporated herein by reference):

    1 mkdsnrcccg qftnqhippl psatpsknee enkqvetqpe kwsvakhtqs yptdsygvle    61 fqgggysnka mvrkafrhga tritafiggq spspklqipg llhgcgsifl dislknqeiy   121 lctwllamrl gnwtpl

An exemplary human TRPM1 nucleic acid sequence is set forth below (SEQ ID NO: 165; GenBank Accession No: BC058286.1, Version 1, incorporated herein by reference):

    1 ggggtccctg ccctggccaa ggaggaggct gaaagagcct gagctgtgcc ctctccattc    61 cactgctgtg gcagggtcag aaatcttgga tagagaaaac cttttgcaaa cgggaatgta   121 tctttgtaat tcctagcatg aaagactcta acaggtgttg ctgtggccag ttcaccaacc   181 agcatatccc ccctctgcca agtgcaacac ccagcaaaaa tgaagaggaa aacaaacagg   241 tggagactca gcctgagaaa tggtctgttg ccaagcacac ccagagctac ccaacagatt   301 cctatggagt tcttgaattc cagggtggcg gatattccaa taaagccatg gtgagaaagg   361 cattcagaca tggtgccact aggatcacag ctttcattgg cggccagtct cccagcccca   421 aactgcagat acctggtctt cttcatggct gtggctcaat cttcctagat atttcattga   481 aaaaccaaga gatatatctg tgcacatggc ttttagccat gaggcttgga aactggacac   541 cactgtaaag aacatctagt gtcccgtaaa tccataccaa agctctgaat ccacaaacca   601 ggctctggcc caaccctgca aacacactcc attgctccat cttcagtaaa ggaagacaaa   661 ttcatttttc taataactgt ggacctgcag cccccttaga tgtgttgaga gtctttggaa   721 atattttcct ctgaggtctg tccacagctt ccctgggcct gcgctcagct ggcccgagaa   781 ggaccaaggt ccctcacatt tgcatgtaaa cagggagtgc cctctgccct tccagtgagc   841 cctgccagcg tgggggaggc ttcagctctg tgatccgttc cagctcactc tgaattacac   901 tcctacatgc ccagtcacag actttttgca atttcatttt atttcactgg cccaacatca   961 ttgttaaaat aaaatttagt tgtgttccaa atgctcaaaa aaaaaaaaaa aaaaaaaaaa  1021 aaaaa

An exemplary human CSAG4 nucleic acid sequence is set forth below (SEQ ID NO: 166; GenBank Accession No: NR_073432.1, Version 1, incorporated herein by reference):

    1 gggaagcagg cgcaggctcc gtgaggaggc aagaggaaag gccaagaact gacaaattaa    61 taaagggcca tctacaagcc aggaataagg ccatcaccag aagacaaccc cgccagtcct   121 tgatctggga cttccacatt tcaaaactga aaaaagataa atttctgttg tttcagctac   181 tcagtcaatg gcattttgtt atggcagcct aagctaagac ataacctcag cctgctggcc   241 tgccttcact gtcctggggg aggcatggag agaccaggtg gactggagta gactgttgag   301 agacactggt ctggtgaaga tgtccaggaa accacgagcc tccagcccat tgtccaacaa   361 ccacccacca acaccaaaga ggttgccaag acaacccgga agggaacagg gacccgtcaa   421 ggaagttcca ggaacaaaag gctctcccta aaagaccgcc gcttcaaaaa aacctgagga   481 atggagtggg ccaacactat ccagccactc cgaccagcca aaagaactca atcaaaatga   541 gacacagtag gaccacaagg gcaaggagac caccaccttc tccagtctct ctttgggcag   601 ccagtaattc ccgggcaagg ccagaaacct caaggctacc tgaaaagtct ccagaggtct   661 aaccccagaa aaatagccaa cagggtgtag agtacatttt ataccccaaa gggtataccc   721 catggtgacg aaaataaaat gaacatgttg taaaaaaaaa aaaaaaaaaa aaaaaa

An exemplary human AC093787 (RP11-215P9) nucleic acid sequence is set forth below (SEQ ID NO: 167; GenBank Accession No: AC093787.1, Version 1, incorporated herein by reference):

    1 tagttgcttc actttccctt gtctagaaaa gattgctgta gtaattatta ttaacactct    61 taataataat ggtaaccagt aataataact gagccttttt acatcccagg gttagtatta   121 taattggtgc cttatgtatt aattcttctg atcctcacca gaggaagctc acaaaggtaa   181 ctaactggct aagcctctca taggcagtag gtgatacagc ctgaagaacc cagatggttc   241 agctcctgaa tccttcttct taccattatg ttctgccacg tctcacatac cagtgggaat   301 ccacacagca gatgaccctt aactttgttc tgtaaaaatt ccatagtagg taaaataagc   361 tatcacccaa ggggtttctc tactctccaa tacagaaaat ggacattagc ctagtgatac   421 caaaatgcta ctgctcttcg tgtgaaatcc tagccagttg aaaccattaa aggggacaaa   481 tgtcactgag catctactgg atgccagaca ttatttcatg catttcaatg tgatttatct   541 cacttagtca aaaaaaaata tatatggtaa atttgaagaa tggttaaaga agtgggtgaa   601 cagccttggc attttctcaa cactataatt tttttggttg tttactttgt tttttcttgt   661 aattaagtaa taataaaaag ttcaataaca acagctcact tttttgaaga atggttaaag   721 aagtgggtga gcagccttgg cattttctca acactataat ttttttggtt gtttactttg   781 ttttttttct tgtaattaag taataataaa aagttcaata acaacagctc actttttttt   841 tttttttttg agacagagtc tcgctctgtc ccccaggctg gagtgcactg gcgagatctc   901 agctcactgc aagctccacc ttccaggttc acaccattct cctgcctcag cctcctgagt   961 agctgggact acaggcatcc gccaccatgc ccggctaatt ttttgtattt tttttagtcg  1021 agacggggtt tcatcatgtc agccaggatg gtctcgatct cctgacctcg tgatctgccc  1081 gcctcggcct cccaaagtgc tgggattata ggtgtgagcc accgtgccca gccaacaaca  1141 gctcactttc aaaatgtatg ttactcttta gaatgtattc aatcactaat ttttgctatg  1201 tgcgagttgt tcttatagtg gccagagtcc ctcttcaaat aggtgataaa atatcttaaa  1261 gtatgtgaat attcatatgt ctcaagttca gttaacaaac aaatataatt agattaagcc  1321 ttgatatttc taatagactt ctctaataaa tgtattttct taatttctac tattattaat  1381 gctttttatt taaaattgag gatgtgatac ataagaaata aatataacta gagccttcat  1441 atttctaagt tttctctaat aaatatattt ccttaatttc taccactatt aatgcttatt  1501 taaaattaag catgtgataa ctatttgttg ccacctcata caaaataaaa taatgtaata  1561 ttaattatgc ttattgtgca tgtgctttgt gtcgacttac ggtgtaagtt gtctagtagc  1621 tcagttagcc cccacttgcc aaactatgta gtcataccaa tttttttttc agatggataa  1681 agggaggcag gagggttttg taaccacaga gttcatcatc agaggtgaac aggaccaaga  1741 tttgaacctg acagtttttc ttcagagttg gaaatcttaa tctccataca tacttgaggt  1801 tttcggatcc tcaccaaatt ttcagttatc taacttaaat acggacaatg tgaaggtcac  1861 aaaattactt tcagtcatct ctaagataaa tctcagagag ataagcaatt tttcagcaga  1921 tgaaatataa ttaaaacaag agattacgta ccttctggtc ctgttgccaa gagatcactg  1981 gtttccccca aggcttgatc tattcatgag ggcagacgtt ggaatacttc gaatttctcc  2041 tcatctaggt aagcttcggg atgcattatg gcaaccagaa taattttatt caagaatagg  2101 aaaggccagc tagtttagca cacttagaca tgaaatttac tattatcata tttaattcaa  2161 tcttatttct tttctatttc aatttacaga tagaaattat agagtagttt tataggctga  2221 cctgtgtaaa ctccttctca taatttttta atacagtcct gaggattcta tacaataatg  2281 taattgtgtt gcctgccatt caatgagtaa ttggccttca ggtttctctt aatgatggta  2341 aataagatgt tacgatttcc tttgttttct gtaagatatt taataatgaa tgtctcaatc  2401 taccacaatg tttaactttg gggaacaaga tctgaaaaaa atatactctt aaaaacttaa  2461 atgttgaatt attccttcac atgtaatgtc ctgacactga tgtttctacc agcatacagg  2521 gagtaaatat tcaaaatgat tgcataaatg tatacaaact agaggctagg aactggtaag  2581 ccttgtccag atgacaagac actctttgct aaaattaaca ttctctctca cctcagaggt  2641 ttcatcattg ctattgttgt caatattgct gtttattaaa actgtattct gtaaattacc  2701 agtgagagtg agtggtttta atattacttt agtgtccaca tagaaattct tcagtgatga  2761 gaagacccaa aagattgctc actgtacagg gactcttggc tagctaaaaa aaaaaaaaaa  2821 aaaaaaaaaa aaaaaagcta aatatttcca ttgctgagat gtaaacgaag aattcccaaa  2881 catttgaggt atctgtttaa tgtctaaaat aagaagttga aacctttcac taacaacttg  2941 tgctgtgaaa cacataagtt taaatgagta attcaacagt tactgtttgg atttacatag  3001 aaagactttt gccaaagcct gtgctgaaca catatcaaaa caattatgcc tagcatgtac  3061 acagtgataa gaatgttttc ttttggcatc cactagagga gaaacttaga gcagcaccac  3121 tttctgccgc tacccttggg tccatgctgc ggtagttact tacctgaatt gtcctcggag  3181 taactgcatt tccttgtata tgaaatggac ctaaagtaat ggatttgccc attagtgaat  3241 aatattagaa acaatttcaa ttgtaatgca attgctgttc agttccatgc aatttctgca  3301 tagaaacaca actgaaagaa aaatgacaac caatcaacca gtaaaacggc aataaatact  3361 ttttaggtga gaaaacgtca aaagagtgtg gatttggaag tccttccatt gtgctaatta  3421 tcgatctttt ttctctctct gaacacttgt caacagtcat taggtttata caattttctc  3481 tttttaatgc atcaaaaaat caccaaatag gaagaagtaa atctgtataa cgggacatct  3541 aacaattggt tttaaaatac ataacctaca gtctaaaata aagaagaaat atatacatgt  3601 gaagcttttt tttgactgac tatattataa aatatgctaa aattgtactg caaatgaact  3661 ctcctcacct cccaaataat aacaaaacat acagtgaaac aaaattgtac aagtttatat  3721 taaggctctc aaatttaaac taagcataaa aactgagcaa tttatcttgg gattctaaaa  3781 aataaaaatg aatctaacaa aattcaaatt gatgataccc gacatgttgt cataatataa  3841 caaagtttac tctctgaaga aatatcaagt tttaaaaata aataggaaca aaaccaagca  3901 tcatctaaag gccagtttct agttttctca gcaccatggg taacttttgt aagaaatgag  3961 ataatcctgt agtcccagct acttgggggg ctgaggcagg agaatggcca gaacccggga  4021 ggcggagctt gcagtgagcg gagatcgcac cactgcattc cggcctgggt gaaagagcga  4081 gactccgtct caaaaaaaaa agaaatgaga taattagatt taccgcaaat gaaattttga  4141 tgaagtgcta ttgaagtata atattctatg aaatcccttg ttaccttgaa aggagctaaa  4201 tgacaactgc ttgattatca tgggacaaag ataactttag gtttttttct tctaaattgt  4261 ggatagtgac tatttcggta ttttctgtaa tggtattttc tgtaagtgat attacccagc  4321 ttttaggtcc acatcttagc caaatcactt cctgaaacct gacttacaac aaaaaccttc  4381 tttgttcttc cttagcctgt gaatagtggc agcatttaaa attaatacca tgcaattacc  4441 ttctgttcta tgataatctt tcatattttc tcttgttttc tcaaactctt cataactctt  4501 aggtcaaatt tcatgcacta tatagttccc ttccttttgt atcaccttta tgtagctaag  4561 attatagtaa gttgttaaca agaatttata gatttatcgg tcaaattatt aaccgttcaa  4621 caagaagacc aaagccaatg taatattttt aaaagtaggg attaagaaaa ttacctttgg  4681 tattatcctt aaagagagtt ttagtcctta ttttccaata catacactca actatacctc  4741 ccgttttgta agaaaaccac ctgcattagg gaacatttct taaattgttg aagtcttaac  4801 attgatacat ttaactattt acttacaatc tttgggaata ttatagagga tattcactaa  4861 agataattaa agagattgta ctccacatgt cagatgaatg gctttaaaac cttagtagaa  4921 ttcaccagga tttttgctta aagtgcaaat ttctcagtta gttccaagtc cagagattct  4981 gatttaacag gcatagaaca ggacctggga atctgcattt taaataaact caaggtccat  5041 cttaaatgca ctcagaaata agtgatttta ctacttgaga aatgtaactt gaggagttta  5101 aaatctgtga aatctgtgat aaaaattaat tatgtggctg ggcatggtgg ctcatgcctg  5161 taatcccaac actttgggag gccaaggcag gcagatcaca aggtcaggag ttcaagacca  5221 gcatggccaa tatggtaaaa ccccgtcttt actaaaaata caaaaaaatg taaccaggtg  5281 tggtggctgg tgccagctac ttgggaggct gaggcaggag aattgcttga accggggagg  5341 tggaggttgc agtgagccta gattgcacca ctgcactgca gcctgggtga cagagtgaga  5401 ctccagttca aaaaaaaaaa aaaaattaaa tatgtgcttt ggcactttaa agagaagtaa  5461 ataaatgatt cgtgtttggc ttctattctg tccatctctg ctaattttct ttctttcttt  5521 attcaccttg gctggtctgt gtatttacat gtaactttca tgaaaactcc atccatcttc  5581 atcaatacac ataatacata ccttgcaagg ccctttttag aagtcctatt caaatatttc  5641 tgagccagat gaatcagtct gtgttagtct gttttcatgc aaataaagac atacttgacg  5701 ggtcatttat aaagaacaag tgatttagtg gactcacagt ttcacatggc tggggaggcc  5761 tcacagtttc acatggctgg gaaggcctca caatcatggc agaaagcaaa ggaggagcaa  5821 aggcatgtct tagatggcag caggcaaaag agcttgtgca ggtgaactcc cattatgaaa  5881 ccaacaggga cttattcatt accatgagaa cagtatgggg gagaccgccc ccatgattca  5941 attatctcca cctggccctg cccttgacat attgagatta ttacaattca aggtgagatt  6001 tgggtgggga cagagccaga ccatatcaca gtcccataat ctcttttgta gtgataaaaa  6061 tcacaagtct gaaccattca tgatattttc ttatactata atttatgaaa gacttacgga  6121 agattttttt gtatctcctc caccttcact attgcaatgg attaaatggt tgtttttctc  6181 cccccaccca aattcatatg tcaaaatcct aacccacaat gtatggtact aggaggtggg  6241 gtctttggga gcaaattaca tcatgagact ggagcccatg tgaatgagat tagcaccctt  6301 ataaaaaaga ccccagagaa ctctcttgct ctttttctat tgtgtgagga tataaagaaa  6361 agacggcagt ctacaagtca gaagagggtc ctcacaagaa ttaatccatg ctggcactct  6421 aatctcatat ttctgaactc aagatctgtg agaaataaat ttctgttgtt tataaaccca  6481 tccagtttac aaagtgccta gtctatggta ctttgctctg gcagcacaaa ctaaaacaac  6541 tatattttta agaaaaaaaa aatgcatgaa catacatcta taaaagtctt caacctgata  6601 actctgaaat aacttttact ttaatggtat tcatataaga aagaaatgta tgaagccaaa  6661 ataaatctca aaattaaggg ggaatattac ttaccaaaat gcatgtttgc tttgccaaag  6721 cctgaaactt ttttcttttt aagcaaattg aaaacctcaa agatttcaat attttttatt  6781 acttatccca gcaaaatcat tcagaccact tatttttaaa attatatagt cactgattta  6841 tttcactttt atgcagttag gataggaagt ggaggtcaat tggaaaatat aattatagga  6901 ataggaccat catgaaatga ttttttaatt tattaccatt cagagcatct atacttgttt  6961 gtcacacatt cagaagaatg gaagaaagga gggtagagaa tgagtcatat gcattgaaaa  7021 ttattattca gtttcaaaat gagtgcccaa aactatagac actgtaagac actgaatttg  7081 aatattttac atttcattct tctattaaaa ttcatttcat tgagaacaaa aagaaaacaa  7141 gaaaaaataa gaagataagc atcttcagag aaacaactac agcccgaaac catgaactga  7201 gaagcaaacc ttccaaatac tgttatattt caactaaaac aaggagtgat cagagtgaat  7261 gctttcacat gtataatcag tacatgttca ggatggtcat tttttccagc tatcattgcc  7321 actactctgg gagatgtaac tcaaaaacta tttttcttaa aattgttaga ttttatggaa  7381 taatgtgacc atgatattaa taaaagtagg aaagtcacta tagagtaact cagtgttgtc  7441 taaccataaa atggaaagaa tttgaagttg taagagaatt caggctgatg tactctattc  7501 atttcatata ctctgagttc caaacagaat gaagctcaca gaagtggaga ggagcaaaag  7561 agaaaagcat taaccagcat gtgataatat agagattaga aatgtagatt tagaaaccta  7621 ggaatctaaa tatgagccac attaccttta gaaaagtgaa tgctgatagg aggagaaaca  7681 agtgtccagt acttagggag taaggaaatt agtgtgacag tattccatta caaaaacatg  7741 gatttaaaaa aaggtacaaa ctgcaatgcc acaccgctcc tgccccagag gatcccttag  7801 ctaatacctg gatctgttct atgaggaatg cagagagaaa aaaatcagta aaatatatat  7861 gcctggtgtt ctattttcta aatatgaaaa tgaacaaaaa gcataaacaa gatgcagttg  7921 ctaaaactaa atcacaagta gaattaccaa agtaatcaga gaacaaattg aagttaactt  7981 aatctcaatt tagaaattga agtgaacaac taaggaatta tataaaaaag aaatacatag  8041 gcactataca tcagcaatta catccagaaa aatagtgaat atctagaaga aaccacacaa  8101 aagtaaatta tatgaaaaga caaaggcata ataaaaatcc ttaatatggc attggtaaat  8161 atagatgcat gacaatggag actcaacctc tgcctacttg atgttttgaa gaataagaaa  8221 gaacattaat actggaaaca ttacttgttg aaaacttcaa agagataaaa tgacacttga  8281 atctatagat taaaatagca ttctgttttt tagacaaaaa tatagagata ctgatcatca  8341 ctaagactga ctttgattca cttactagat ttgaagaata aagcaatagg ataattgtca  8401 tctgggcagt taaacaagtc tctgagaatt caactgttgc cgataaagaa ttaatgatta  8461 ccagaattat gcaacttttg taaacgtcta gaaatccaga acaagtatat aaactgtttt  8521 tattgcatga aaaaaatagg cagcccaaaa ctgtcatttc tgagagaaag aaaacaatat  8581 atacccttta ttgtgccagc atacttactg aaagtgattt ccagcctcca gcatggtatg  8641 agacaatccg agagagaata tcatgatttg ctgaatttaa gagcaagata tcaaagttta  8701 tgtaggccaa ggtgactaga atcatcaagg cagactgaca gagagaagag ggctgcacag  8761 agagagaact gtggagattt acatagaggt tctctggagt ccttgagtga gaactgaact  8821 gtgcctacat aaagtaaaac tccatgagat agaaaaatga gtcttcatta gcaatgggcc  8881 agagaaattc ctggaggtca tatgggcctt agaagaaccc gtatgtgctc cagccagagt  8941 gagaaactta taatagcaga tagagttctc agaataatca caccttagta gcggggtgaa  9001 tcagttctag agtcaaggct ctgaagccat tataatcaca tttaaaagca aacaatatca  9061 ccattgatct cagataactt aactgcattt gaaaacaaag ttcatctctc tttaaagaaa  9121 taaaacaaaa tccagatcct aacaatgtag aattcagaat ttcccttaga cattaaaaaa  9181 ataacagaaa tgcatataaa caaaaaaatt gatccaaaac aagacaaaaa ttaatcaaaa  9241 cagaccaaga aaagatagaa attatgggat tagaaaatat taagcagctt aacaacacac  9301 ataattgaaa tcccaggaaa tgggggcagg gcaaaaacta cttgtaaagg tagtggttga  9361 gatattttta aaacttggta aaactataaa ccaacaggta aaagaagtgc agtggactca  9421 aagcaaaatg aataaaagga ttaagttgaa gaaagttgtt tttaaaaaga aaacttaaaa  9481 acagttggag aaaaagagat gtattactga caatggaacc aatgtaataa ctacttttta  9541 tgataagcat gtatatcaga agacagtagc gcaacattct attacttaaa gcaagagaaa  9601 caagtcaacc tggaaattca ttcaagtgaa aattctaaaa aaatcaagaa atttacaaaa  9661 atgaaagcaa ataaagctat tttgacaata agtagctgat agattttatc aacaacatac  9721 tgggactgaa agaaatggta gacaaaaaga aagtaacagg atgataatgt acttttttta  9781 ttattatact ttaagtttta gggtacatgt gcacaacgtg caagtttgtt acatatgtat  9841 atatgtgcca tgttggtgtg ctgcacccat taactcgtca tttaacatta ggtatatctc  9901 ctaatgctat ccctcccccc tccccccacc ccacaacagg ccttggtgtg tgatgttccc  9961 cttcctgtgt tctcattgtt caattcccac ctatgagtga gaacatgcgg tgtttgtttt 10021 tttgtccctg cgatagtttg ctgagaatga tggtttccag cttcatccat gtccctataa 10081 aggacatgaa ctcatcgttt tttatggctg catagtattc catggtgtct atgtgccaca 10141 ttttcttaat ccagtctatc attgttggat atggggtaaa ggattcctat ttaataaatg 10201 gtgctgggat aatttacatt tttaaaaaga aatgattcat gttagaaata atacataggg 10261 cagtgcatgg tggctcacgc ctgtaatttc agcactttgg gaggttgagg tgggcggatc 10321 acaaggtcag gagttggaga ccagcctgac caacatggtc aaaccctgtc tctactaaaa 10381 atacaaaaat tagctgggtg tggtggcacg tgcctctaat cccacctact caggaggctg 10441 aggcaggaga gtctctcgaa cccacgaagt ggaggttaca gtgagccatg attgcaccac 10501 tgcactccag cccgggcaac agagcaagac tccatctcaa aaaaaaaaaa aaaaaaaaaa 10561 aggaaaaaga aacaatacat acaaaagaca ttttttcatg ttttaagtaa tgttaaaggt 10621 aatggattat ttaaaaccaa aataataatt atttctgtgg tattcaaaat atttataaag 10681 aaaggaggaa aaccctatga cagtagggca aagaactgta gagagaaaat ggatagacag 10741 ttataatatt tgttttttta tttgaacatt tattttaaat ttatggaaca catgtacagg 10801 tttgttacat ggatatattg cgtgatgctg aggttggtgg tacggttaag cccgtcgccc 10861 aggtactgag catagtacct aacagatagt ttttcaaccc cggtctccct ccctcccttc 10921 ctctccctct agcagtgtcc agtttctatt gttgccgttt tcatatccat gagtaccctg 10981 tgtttaactc ccatttacac gtgagaacac gtggtatttg attttctgtt tctgcattaa 11041 ttcacttaag ataatggctg caagttgcat ccatgttgct gcaaatagat ggttttgttc 11101 tttattatgg ctgtgtagta ttccatagtg tatatgtacc atattctctt tatccaatcc 11161 actgctgatg ggcacttagg ttgattccat atctttgcta ttgggaatag tgctacaatg 11221 aacatacaag tgcatgtgtc tttttggtat attttcttat ggatatataa ccagaaatgg 11281 gattattaag tcaaatggta gttctgtttt aagctctttg agaaatctcc aaactacttt 11341 ccccatgggc tgaactaatt tacattccca ccaacagtgt ataaacattc cccttcttct 11401 atagccttgg caggaacttt tcaataaaat atattattaa acatttttgg agcttttatt 11461 aatagccatt ctggctagtg tgagatgata tctcattttg gttttgattt acatttctct 11521 gagattagtg attacgagca tttttttcat gtttgttagc cacttgtgtg ccttcttttg 11581 agaagtatct gttcatggtt ttgctcattt ttaaaattat ttgttttttg cttgcttaat 11641 tatttaagtt ccttatagat tccagataag agacttttat tgaacacgtt gtttgtgaat 11701 attttcgccc atgctgtggg gtgtttgctt atgctgttga tagtttcttt tactgtgcag 11761 aagctcttta gttgaattag gtcccacttg tcaatttttg ttttgttgaa attgctttcg 11821 aggacttagt cataaattct ttcccaaggc tgattttcag aatggtgttt cctagcatta 11881 cttctaggat tcttatagtt tgaggtctta cattgcagga ttataggttg ctgggtttta 11941 gtatcatggt aatgctggct tcagaattgc aatattttaa aactatatag caggtattat 12001 aaatattatt tgaaggttga gtgttttaag ttaaaaaaaa tgtacagatg gtactcttta 12061 tgcacatcag tgcggggcct tagtaaccac tgtgcaagtt gaaactgggc aaagttatct 12121 taataattac tggaaaaaca taaacttgtt cctgcaatca ttaaaaacac ttgtcagtca 12181 ggtgcagtgg ctcgcactgg taattccagc actttgggag gccaaggtgg gcagatcact 12241 tgagcccagg agtttgagac cagtttgggc aacatgacag aaccctgtct ctacaaaaac 12301 tacaacaaat tagccaggag tggtgatacg tacctatagt cccagctatc caggaagctg 12361 aggtgcgagg atcacctcag cctggtggtc gaggctacag tgagcctttt tgataccact 12421 gcactccagc ctggacaaca gagtgaggtc ttgtctctaa ataaaagaat aaataaataa 12481 acacatttgt caaaatatta aaaatgtctt actgttggtt atatatgcat agaaaagtaa 12541 aaaccaaaaa acaaccctaa aactagtatt tacatagtac actataattt aaaacattga 12601 taattaaaat acatgtttta tatatttctt tgaaatgtat tcagattagt ttgtacagta 12661 tttgtacaac ttctcatcat gtgactctca atatttttta tgctttggtg aattgccata 12721 cttctttata aatttgatta tttgtccaac attttattgt ttgtgcgttc attgtcttta 12781 aacatcttgg agagtttctt caatgtaatt ttttttctca gcatcacatc ttctgggaaa 12841 actttcgtct tttccctgca atcagcttct tcatttaagt tgtaaatatg tattccataa 12901 gttcccctga ctgcacatat gaaatctctt ggatggtagt tgtgtcagca ttctcgcaat 12961 taactatttc ttctataaat ccatcaagat ccgatctgaa ttcactttcg gtgttgacac 13021 tttcatttat ttgccacact ttcatttttg ttggctgatt ttctgtcgtt tatcaatttt 13081 tgtgtaatgt cacgtcttta tcactgaaag acaaagaagc aacactactg tatgctttcc 13141 tatctctgta tgaatacaaa acagatacat agtaattgat tattgataga tattgagaaa 13201 agtgacatga ctaatcatgg atcttgatgc aaatctgaca tttacctaat agttttatgg 13261 actgaagagt taacagaaaa aaattgtact tcaagccatt agtcccaatt aatacactgc 13321 tgtacctaca ctgttttgtt ttggggcttg tgctatgtaa ctaaagcatg ataactaaag 13381 cctttgcata tcaaaactaa ggaaaacaag aactgtctat tttatgagcc ctatatcaat 13441 cattaaaatt aaaacaatgg aatggttaaa agctaatagt ggagataaaa gcggatctta 13501 aaaactaaat tttcaattca aaagaaggca gaaaaagggg gaaaatgaac aaaaatgatg 13561 agacatttag aaaacatata gcaagagagt agttatacac ccaatcatat tgataattgc 13621 attaaatata aattgacaaa atattcttat taaaaggcag agatcataag acaggattaa 13681 aaaccctgac tcaactatat gctctttata agaaacttac ctgaaccaaa aaaaagaaaa 13741 acaaacaaac caaaacccac taaaactgtg aagagcaaag taggcatcag aacaggaaat 13801 atcactgggg atgaagaata acatttcata atgacaaagg ggaaaataca ccaagaagac 13861 atgtaaataa taaatatgta tgcacacaat agcattactt caaaatacat aatataaaac 13921 ctattaaaac tgaaaggtaa aatagtaaaa ccacagtcat ccatggggat ttcaacagtc 13981 tcctgccaga aatttttaaa atttgttaaa caaaaaattg gtaagggtag agaggatctt 14041 aaaaatacaa ttagccaact tgatctaact gaatctttta gaataatcta aggatgaggg 14101 atgaggtagc agagaaagaa aaggcagaca tcaatgtgac attactgttt caaggctatg 14161 agaatacacc aataattgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgcagatggt 14221 aagctcaatc ttaaaaatgt tgagttttaa ctgaaaattc attattagga aagataagag 14281 gagatgatat ctagtgagag gctgtatgac tgaactctaa gagaaaggtc acagcagaaa 14341 ttgtgtacct gacagctcta gaaggaggtc agtcaaaagt aagtcagtga tgaattctct 14401 ggtgtaaaag cagaggaatg aggattagat ttaaaacaca tggaagcaga gtgacttatg 14461 ataaaaacat gagcttgaaa atcctgcaga gagggcttta aatcctgggt atgatatcct 14521 gcttgtgtag gcaatagtga taaaaacaca acaacaaaga gaggtaaaga gcactttcct 14581 ttgatataag taaagggcac gacttattgc acatatatat ataggtattc aactgagatt 14641 caacatgttt ctctcattga aacagcaagc tctccaggcc ttcatgttcc cagtgaggta 14701 ggtacccttc tgatgattat actcaccctc cctcattgca aagctcccgt tgttattgtc 14761 ttggctctgg attccctcaa aaatagacta tgaaacaaat atctggggtc agatacttta 14821 atcagaaatt gagtgagaaa gcacagaagt ggagaaaatg aaacagaaca cgaagccagt 14881 gtgaatgagt agttactgct atgtgctcag taatgacgga ggtatggaga ttgtctcaaa 14941 ataactttac aaagagatgg ggatgctgga atccccatct cttattgctt aaggattacc 15001 ttagaatcat taactctcca cccctaactc cttctttgtt cctatgtgtg gttgagaagc 15061 actggttagc ctcaagaagc ttgcaggcag gtccacaaat cagaaagaca ggcatgatgt 15121 ggggagctct cagttagctg gaaacaggtg aatttcaggt gaacacattg agtccaggac 15181 atagaagaca agtcatcaac aatatctgct atagccagtt ttctttttct ataacacata 15241 tactttttat tgggggtccc caagtccccc tttggtttaa tgattcacat aactcaagaa 15301 agctgatttt ttttgtggtt atagtttcta acagtgaaag aaaccagatt aaaataatca 15361 gaagcataaa agcacataaa gttgagtcca ggacaaacca gatatgagct tacaggtgtc 15421 ctttcatagt ggggacttca cactgactaa ttttctttac aatcatgtga gacaacatgt 15481 gtgaacttgt tgccaactag ggaagctcag tcagtcttga gtccagggtt tttattagga 15541 ttccaccaca tatgcatcga gcatcctgtg actgaactta gctacttagt tcccaacctc 15601 cctatgccct gagaggtcat attaatatgg cattacacaa agtcataggc atacagaaac 15661 aggtgctcac aagaaataac gttgttagca tcagctattt ggtatgacct acgttttcaa 15721 gtatacaaag actctcatca ggcagcatat accaagggct cataggttgt catctcccag 15781 gaggttgtca agggccagtg ctgaagacct ttggaatgcg caaggttttg gaaagccatg 15841 tctgcagaat taaccattac acaccttcca agaatttttt ttctctttaa aaatgttttt 15901 tgatctttga caatgtacca accaagactg agtaattagt aacagcagtg tactcctgag 15961 tacttgcacc tgcaaggaga aaaaggacag atgcacttac ataggacaga tgcaaataga 16021 caccactatg acaagtaaag ctggaataat caataaattc ctaaagacaa agtggggctg 16081 gtcagattgg gagaccgctg acagctgcag aagttgggaa agatccatca tcttgaaaac 16141 tttttcccca caaacccact gcgatctctc aagcaattgg taaggaatcc aagagagtct 16201 gtatatgaca cagatcaggg agagcagaac acttgggagg tgaccaggtc ttgggggctg 16261 agcccttatg aatgggatta gtgcctttat aaaagaagct caatggagtt cttgtgtgcc 16321 ttccactatg tgaggacata gaaagaaggc accatctatg aaccaagaaa tgggctctca 16381 tcaacactga atttgtgagc atctttacct gagatctttc agcctcaaga agtgtgaaaa 16441 aagaaatatc tgttgctttt tagtcacccg gtttatgtta ttttgttata agagtccaaa 16501 tagaccaaga tattccattc cacttaatat gtaggggaag acaacaaaaa ctgccacact 16561 tagaatactc ctgatactgg aagtatgaaa acaggaaaaa caaaacaaaa ctgctcttga 16621 aggtgaagga ggaatatcac tgagctcacc aacacagcca ggaaaagaac agaagtgtga 16681 gaaggctaca ttcctgagac cctgagaaaa agtacctgca taagactgag atgaaattac 16741 ctaccctagt tataattgaa atcccaaaaa gaggaaaaaa taatggagca aaagaaatat 16801 ttttcaaaat aactgccaaa aatattctaa aagaagtgac agaaaatcaa acttcagata 16861 taggaaactc agagaatgtc aaatagaaca aaaataaata agaaatacat cttgaaaaat 16921 ctttaagaaa tcaactctaa attttatatc ttgctccaaa tatatagaga tataaatagg 16981 ttagcatgaa gatatggaga aagccatatc atggaaacac taaaataaag ctgtggaagg 17041 acattgatat tagacacaac aaagttcaga acaagaaata gtatcagaaa tgagagataa 17101 tagataatat aataattctc aagatgtgaa catcctacta attagggtat gcagctaaca 17161 acagaacctc caaatacatg aggtaaaaca ggaaagaaat caaaggtgaa ctagaaaaat 17221 ccaaaattat atttgcagac ttcaacactt ttgtcttagt aatggacaga ctaggcacaa 17281 actcagtaat cctatggaag ataagaacaa caatatcacc aacaagacac gcaatcttca 17341 atggcagaca cgctttcaag tgaaaaaaaa aacagtatgg catattttct aacaaaccca 17401 gaatttctaa tatttgcggt cttccttcca tcttcctttc tcttctcttc ttcttttcct 17461 ttcttttcct tttttctcct tccttcccct tattcttcct tccctcctcc ctcccttttt 17521 ttccttcttt tcttattctt tctttccttt tttcctccct tcctccctcc ttttcttcct 17581 ccctcccttc ctttttcctt ccttcctccc tattttgttt gccttcctcc cttttaccat 17641 tctctcttcc tttccttcct ccttccttcc tcactttttc tctttctttc ttgagttctt 17701 gctttctttt ttctcccttc ctccctccct tctctcattt cctccttttc tttcttcttt 17761 ctttccttct tttttctttc tctttacaac tcatattatt taaaaaaaat taagacaggc 17821 agaaaaataa agaacacttt aatctgcagg taaatagatt atgtctgctg tagacaaaat 17881 aatggcctcc caaaaatgtt catgtcctaa ttcccggagt ctaacataca aatatgttat 17941 gttgcatggc agtgggaaat tagatttcaa gtgaaattaa ggttccaaag gcagcggggg 18001 caaaaagcct aggcggaggg ggcaaaaagc cgcggcggcg ggggcaaaaa ggagcggggg 18061 caaaaacccc acaaaaaccc gcggcgacgg ggggaaaaaa ccgcggcggc aaaaagcctc 18121 agcggcagga gcaaaaagcc gccgcagtgg ggataaaaag ctgcggtgga aaaaacccgt 18181 ggcggcaggg gcaaaaagcc gtggcttcgg gggcaaaaag ccacagcagc aaaaaccctc 18241 agcggcgggg gcaaaaagct gtaaaaagcc gcggcggcgg gggcaaaaaa ccgcggcgcc 18301 aagggcaaaa agccgcggtg acggggcaaa atgccgcggt ggcgggggca aaaagccgcg 18361 gcgggaaaaa accgcagcgg cgggggcaaa aagctgccgc agcggtgacg aaaagccaca 18421 ggggcggggg caaaaagccg caaaaagccc cgacggcggg tcaaagagcc gcaaaaagcc 18481 ccagcgtcgg gggcaaaaag ccgcggctgc cggggcaaaa agcagcggag gcaaaaaccc 18541 gcggcggtgg ctgcaaaaag cagcggcggc aaaaagccgg ggcggcgggg gcaaaatagt 18601 ggaaatgggg tagaaggcca gcacagcttg gcattcctgg actgtgatgt ggaaggaaaa 18661 gtgcagcgca agacaaagat gtaagtaggc ttgactcagt gcagctaaga actcagatgt 18721 tatcttgatg ttaactatca gctgattttt tgtattttag tagagaaggg gttttaccac 18781 attggccagg attgtctgga tctcctgagc tcatgatcca cacacctcag cctcccaaag 18841 tgatgggatt agaggcatga gccacaaagt gctcaaaaaa tctattaatt aaaaaagtgt 18901 atgtagccgt cttcaatcta ccatgtccat tagcagataa atactacaag caaaataaca 18961 acaatgaaat aaacatagac ttagagtaga tactctgatt taataaaaat ttgaaagtag 19021 accaaattac gattaaaaaa actctgttac tattgaggat gagggttagt gtttggaaag 19081 gggcaggaga agtatcacta tttttagtaa tgttctattt tcatacatgg ctataagcaa 19141 atatatgtgt ttcattaatc aaggtatcca tatttaatca ttgtactttt ctgcatgtat 19201 gatatatgtc aataaaatgt cttaaattat atacagcaaa aatagacaaa accacaagaa 19261 gacatacatg aatgttaaac ctagagagaa atttgaatat aagtaagtct ctgaatgact 19321 gctagaacaa accaaaaaat aatcaggatg gagaggtttg gaacagcatg attagcaaaa 19381 ttgacatatc tgtcttttaa tataggcaga aacatagatt aaaaaaggac ttgtctcaga 19441 gtatgatttc tgaaaatagt ggaatcaagt ttgaatctag taagtacata taaataaatg 19501 tcttaaaact cttatgttag ctaattaaga aattattgta atagatatta gaaaatattt 19561 taatacattg agtggatttc acacgctaag gaaatgatct tacttgcatt tgatagttca 19621 attacataca tatataccta taggtagttt aaaatatttc taataacctt atatactttt 19681 aaaaagcatt gatatctgtt tgcactatct ggtctataga atacacatac caaacatgat 19741 tatagctctt ctgctataaa cttcaaatgt ctaattaata caaaaatcta gaatgagaag 19801 agttctttgc aatttttttt tttttttttt ttttaccaaa tagaatatag gaaggatagc 19861 tgcaaatata cctgacacac ttatctgtga gtatggtggt agccttttta ttttattttt 19921 gagagagggt ctcaatttgt cacccaagat ggagtgcagt catgtgatta gagctcactg 19981 aagcctttac atactgtgct caagcgattc tcccacctca gcctcctgag tagcagggac 20041 tgcaggtgca tgacaccata ctagctaatt tttgtaaaga tggggtttca ccatgttgcc 20101 ctggctgatc tccaactcct ggactcaaga gatctggcca ccttggcctc ccaaagtgct 20161 gggattatag ttttgaggca ccgcgatcag cccagcctta aaaaaggctg actagagatc 20221 tttatctatg tatatctata tctatctata aaataaacgt gtttattata taaaaatata 20281 tattattaat attatataaa aatttttttt caaggtagaa atatataaag agggtgcatg 20341 tagagcctgg gtcattgtgt agtgaagctc aaggcctctg aagaaatgcc ccttgcctct 20401 tttgtctggg ctagaatcca agaagggaaa gcagcagatg cactggttcc caggttcttg 20461 gcatcctaca gagagaaaca tgtttgagct aggatagcgt taaacaccct tcttctcact 20521 ctcctgtttt atgtagtgag cagagactag cttcatgaga acagactgtg acagtcaagg 20581 ctgtctgtta ttttgtgcag cattaattga gaaattctag cacctgaaga cctctgggcc 20641 atttgagggt aggtgcaggg aaggaaaggg aagtttgcat ccctcctgct gtggagagaa 20701 cccgtgggaa gcacagacct tgtcctaact aaaggcagac ccccttgcta accagcttct 20761 catcagccaa ccctgggtga gtttccatgt ctatttacta aataatcctt attgcttttc 20821 ttcatagggg caaagtatgg tttacaggga atattgttcc tttgaacacc cattgtgcaa 20881 actccttcct gttgtgggaa aacaggcttc catatgtgtc tttttgggaa acacattggc 20941 aatttctatg tttttactgc atctatttct tggatatggg aactgaatag tgcccatcaa 21001 aggctcacct gatgttggat attgatctga gagcacggaa ggacagaatt ctttctttgt 21061 tcctgggcag ccgtggttga gggatcattt tgtggcagct acagtggcaa tgatggaggc 21121 agaacggagg gctcagtacc aagacaagga gagacttggc ctcacaatgg cagcattgca 21181 ggggtgcgtt ctacagagca tttgctcaca tggttttggg cattgtctct aactacattg 21241 cttccccaat aggttgaccc attctaaata actccttttc tctttaaaac agaaaacttc 21301 atttgtatga cttgcaattg taaatgacac gaattggcca gttatcattc aaattccctg 21361 ttacttaatc ctgccttttt ctaacgtatg caactttccc ctaaaaaact ggacacttcg 21421 ttgcttattc attgtcttta cacattttaa aatgttgctt tatgccccca atccctaact 21481 acattttcga tgttttgcaa gtggagtcca tgtgttcttg atttacatga agctcaaaat 21541 aatggttata gtaactagta cttcataatt aagcaaaaag ctcttattga aaaatgacag 21601 aactatacat agagatgaca acatggagag atatttcctg agatcacaaa gttatggtat 21661 ggcagaacta gaaagttgag tagagactct gttcccaatc attatttcta ccaccagctt 21721 tctattttga tgttaatagt gttcttatgt gggaaaccct acatatttgc cagtgtttag 21781 ttcattgaca aatataaaga acttcaagaa cactctaatc ttttaaaaat aaaatatcta 21841 taattggcca tatgaaaaaa attggtactt gacatatact gagatcgttt tattttgtgc 21901 tagacaaatg aagtcataga acagaatgtg ctttaaatat tatgaatagt gcttgcgtgt 21961 gtgtgtgtgt gtgtgtgtgt gtgtgtgttt atagatgcat attaggctgc tgaaaagttt 22021 gactattctt tccaggagag agactgccaa cttttgaacc taattagtac aagtatattg 22081 cttcttcata tttttattaa ggcaaagaga gtctagttaa aaataattca acttattgtg 22141 gaaatgctat aaattgctgt gaagtgagtt gctggctatg gcttgtcaga gcgaatatat 22201 tgtacaaatc ttaggggaga attagtgctt atgcattaaa atcaaatcat cttgcagcac 22261 actgagaaaa aggttagatt tttaaaataa tttcagagtc atgaaaagag caaatatgct 22321 caacaaagag cctagcaacc ctcaatgacc aattcccctt ttatatagtt tggtatctga 22381 attagaatcc cagaatctac aaattcctct gggtgtgggt gctgcatttt gaggatttta 22441 taacactgcc atcaccaagc tctcttttga tattcaattt aaggagataa tttacgggca 22501 accagagagc atacaccaaa gtaggtatct atctagatag acagatacat ctccatatca 22561 ttgacaggat actttctggc cgagcgtgag tacaacctat gggtgtggtt ggagagaaca 22621 tgtgttccac ctgaatggca gatcaagatt attccttctc atctgctgca atggctcaat 22681 gtgttaagga gaggagtgag acagcaagaa ctgcattcat tcagtcatac agaccaaaag 22741 gaggaatgtc gcccagccct ctaaactgac ccagaaccca gctcatgtct caactgctac 22801 ctctactact tagaaagaag taactccgct aaagcagggt tctggacaaa tatattttta 22861 ttgatcatat acaaatagat gaagatggac ttggatgtta agaaaaataa tactatacaa 22921 aatcaagagt agacagtcac ccctagactt aaattaagag tgtgtacatt agataattta 22981 atccaatgta tcaggtaaaa acttgaacaa acgttttggc ctcttccata aaattcaggg 23041 aagcatgtcc tccacaaaac agaatcaaaa tataaatgaa agactggctt aagatgaaag 23101 gaaaccttat aaatgaaaag aagccagatg agaggcactt aactgagaat gaaaaaaaac 23161 tgagtggaca aaataattat gagaagatga atcttcaaat cagaaagagg gaaaaaagct 23221 catttgatac tatgggaact caaaagagag tgaacacaaa tgtgaaaatt ccaagagtac 23281 agaaaagtag cataactaaa ttaagagcat gagaaaatgt atacaattct gagtaataag 23341 aacagaaatc aaaagttagt attgtatgtt ttagtagagc aacactgaag acgaatgaaa 23401 acaagaaata atattaaata tgaacatatg gagaacagaa caatattttt aaaattttta 23461 gtttctaagt ttacctgaaa ttttaatttt ggtttcttat gtaataccag agttattagg 23521 aagatattag ctaataacac tattttcagt ggtattttaa gtatttgtcc tagaaaaatt 23581 tctatttttt aaaaatgtat atttaaaaat acattaaatg tgtatataca tcaatcatat 23641 gtatcgattt ctgttttttt tgaattgcaa atgaaatttg tatttttgtg ttcctggaat 23701 aaaataaact tgaatggatt gtgatatatt attcatgctg taattcaatg tatttgaatt 23761 ctttaagaat gttacattta tagttaacag atattgacct ataaattttc tttcatataa 23821 taatgctgtg agacaatata agaagaatta aaatttaaat tcatgtattc ctactttttc 23881 ctctgttctc taactgtaat atattttaat tacagatgga ggaacagata gatgttagat 23941 aaataggtat ataatagatc atccaaaatt cttattgttt tatgtagtca gtatttacct 24001 ctgtttttct acatgtttat ccttccaatt tagttcatta ctttctgcac ctttgatgtc 24061 atatacataa acaggaaata acacatggtg gccgggatgt agagagagcc acaggacttg 24121 tgaatacaat ccacaggcaa ggatgtggcg attccttttg cagtattgga gggaatgcca 24181 aacgctatgt ttgctgtgga aaagagtatg gtagttcctc aaaacatcaa aatggtattg 24241 ccatatgatt cagcagcgcc acatctcagg atagcaaaag aattgaaagc agagtcttga 24301 aaaaatattt gcacatccat gcttgcagca gcgttattgg caatagctaa aacgtagaag 24361 aaattgaagt gtccaacaac agatgaatgg ataagcacaa tatgatatat acacacaatg 24421 gaatattatt cagccttaaa catgagggaa atattctgac atatgttgca acttggatga 24481 aacttgagga tattatgcca agtgaaataa gttagtcagt gaaggacaaa tacagtataa 24541 ttccatttgt attaaagtgg acagaatcat agagatagta caatgatggt tgccagaagc 24601 tgtggggagg aagaaatggg gaagtattgt ttaatgggta tagagtttca gttctacaag 24661 atgaaatgag ttatggagat ggatggtagg gatggctgca caatgttatg actatattta 24721 gtaccactga actgtacact taaaatcgtt aacagagtac attttatttt atgtgtattt 24781 taccacaata aaaaaataaa ataccttagg aacattttcc tgaaagagtc cacataaaat 24841 tcattttaat gcatgtgttt atgcatagct ttctattttt ctcttttcta tttatattcc 24901 aaattagaat ataatgctaa tcaagcatag tggctgtgtt tcttgcttcg tctagtctgc 24961 aggtagcata caaatgtaat aaactactta ttcatgtcac atctatttat tttctgcctt 25021 ataccaagct tgtgggattc tcttaaatac aacattttta tacttacacc taggcaatac 25081 ccattagcat cgccttccta aatcagggga aattgagcct ctgtaaggtg gagtaactta 25141 ctaagataca aaactcagca ttaaagtctg tatacttcaa tatcctgccc tcttctcatt 25201 tgtctttact gccttttatg tatgtgttag atgttcaata aattctcttt tttaaactga 25261 atttaagccg tggagcagtg ttttgttgaa caataaatat gatataggac actcttcctc 25321 cctttcattt atgatccagt tcatgaaaaa gagaaattct ttcattgtgc tagaagctta 25381 aaataatgaa aatgccactt tctacattaa acagaaactg aagggaatca aggtgaattg 25441 cacgagacat agaaaacaag tgggaaagaa atctagtata atttgccctt tttgtacctt 25501 tattatttgg cgtttgagta aatgtttccc ccaaatatct tcccatctta attcatgtct 25561 atgaagtaga catttatgtc tcaccttgtc aagaagggca aactctaaca taaacatttc 25621 ccaaaaatgc tttctgctaa aacgtaagct cagtctggct agaaatgaag ctcacttcat 25681 aaagattaat tggtagctaa tctttgcatg ctgttctctg aacctgagtg aaagctgtcc 25741 atcaggcata cagggaatga cggaaaaggt gacaacagaa gatgaatgct atgtcactaa 25801 ccttcaaaga tgacctgcct tttctttcaa attcttgata tcttaagact tcattatttc 25861 atctctcttt gcccttggtt caacattgtg ctataccaaa actcatgtaa aacaatgatc 25921 taatgtaata aaaatggcat ttttctttca tgtagatgca agctaactgg catttttaca 25981 atcaacgtat ttcctttgtc aatttttcat tctgtattgg aagtaattga taggtatttc 26041 tgaagggatg aaggtgtttc tgtgttcatt gtgatccaaa ctatttttag acctaggggc 26101 atttgtaaaa caatttgtgc cagctgacca aggaccactg tggcagaaag cagcaaactt 26161 gcataagatg tcactgcctc ataagttggc tttgaaaact aggggcttac tctatagtct 26221 tatgaatcaa agacattgat agatgtagta taagattaca atcatatttt ccttttgaca 26281 gtcacattat aaagcatgat gtattgcaat taatctcaat tagctgatca caattaaaat 26341 taatgtttat tattgctgat aaacaatcat gaatctcctg ttctcaaatg tgcaagtaat 26401 tcttgtaatt ttaatacaaa tttgcatatt attactaatt gatttaatct cattggattt 26461 ggttcatgga tccaatttat taaaatattg gtaatgggat aatgatttgt ctctccattt 26521 catgtacgct aaaagccaca attcttacaa tggtctgcaa gcccatcatg atccgctgca 26581 ggttaaccac gaaaattctt ttatttcttc acccttgatc ttaccagtgg tcctggccac 26641 ctcactgtcc tctggacatg catgtttgct gctgtcttat gaccaagact ctagttaatt 26701 tcttggcttg gaaagatagc cctccatata tccattgatc agctcactca acttcctcaa 26761 gtctttactg aaacctcaca ttctcgatga gacctattcg gtatttcaaa ctgcctccca 26821 gctgcaacat tcccaaaccc cgtactcttc tgtgtatttt tgaaaggatt tattgagata 26881 taatttacat agtgtagagt gcacacatta atgtctacaa gtcagtggct tttagtatat 26941 gcacaggtaa gtggagccat catcacaatg aattttagag cattttcttc acttcaaaaa 27001 gaaaccccac cttctctagc tgttaacctc ctatgcaccc atcccctact caatcctaag 27061 caaccacaaa tctgttttgt ctctatagat tttcctattc tattttcatc taaatagaat 27121 catacaatag gtggcctttt gtgcctggct tctttcagtt ggcataatgc tatcaaggtt 27181 catatatgta ttggtacttt atttcttttt ataactgtag aacattcaat ttcatggata 27241 taaaattttg tttatccaat aatattttta ttgacatttg agttgtgttc agcctttggc 27301 tattttaaat actgctgcta aaaatacttg tgtacaattt gtgtttgaac acctctttcc 27361 aataatctgg gtgtatacct aggaatacat ttctgggtca tatgacaatt ctatgtttaa 27421 tatatttaga agccatcaaa ctgttttcca aagtggccag ttctagccat agagtatcta 27481 actgtggttt tgatttgtag ttgcctgatg agtgatgcta ttgagtatat ttttatggga 27541 ttattggccg ttcgtgtaac ttcttgggaa acacatctat tcctatcatt tatcagtttt 27601 gagttgggat atttgttact gagttaaaac aatttttcta tattcaagat acatatatat 27661 atatacagac atatagacac gtgtttttca aatatcttct cacaattttt gagctgcctt 27721 ttgacttgct tggttgtcct ttgaaacacc aatgtcttta atttttaaga aattttaaat 27781 atctaatttt tattttgttg ctcatgtttt tggtgttaca gctatttctt tgctagatcc 27841 aaaatcctga agattttccc atatgcttta ttctagctct tgcatgtatg tctttaattc 27901 atttgagtta atatttttgt atgctttggg gtaagggttc gaatttatta ttttgcaagt 27961 ggtgatccat gtgtacgttg ttgacccagc ttgttcaaga ctgtctcttc ctcattgaat 28021 tgcacatggc accactgtaa gaatccattg actatagata catagtttta tatatggact 28081 ctccattctc ttccatcaat ctatttttcc ttcatcagta ttgtgttgtc ttgattactg 28141 atgctttgca gtaaggtgtg cagcacgggg gtgtgaatta tcctattatg ttttcttttt 28201 tcaaggttat tttggctatt ttgagtccct tgcgattcca tgtgtatttt agaatcagct 28261 tgtcagtttc tagacagaag tctgttggga tacttttagg gatttcatca aatctgtagt 28321 tcaaattgta aagtactaca atattaaatc ttccaattca tggctataag acatttgcta 28381 attatttaga tcttctttaa acaataattt ttaattttca gagtaaaata ttgtatcaca 28441 ttttccaaat taattattat ttcttttttg acgctattgt aaattgaaat gttttcttag 28501 tttcattttg gggttttcat tgtagatgtg tgcaattgat ttttctatat ttatcttgta 28561 tgctgtaata ttgctgaaat aatttactag ttctgtcgtt cagtggattc cttaaaattt 28621 tctatataca agaatgttat ttgcaaataa agttttattt ctttctattc aatatgggtg 28681 actcatttct ttagttgccg atttgccatg cataaaatct ttagtataat gttgactaga 28741 agaggtcaaa gtatatatcc tattcttatc tctgaccata gcgggaaagt atcctttctt 28801 ttaccattaa gttgcatgtt tgctgttggc ttttcacagg tgccatgtat ctggcgtaga 28861 aagttctcta ttcctggttc attgagtttt tatttttatt tttaatcatt aaagaatttg 28921 gattttgtta aatgtctttt ctgaatctat cgagatgatc atgcaattct cgtttcttat 28981 tctatggata agatatatta ccttaatgga ttttgggctg tttaaccaac ctgggattac 29041 ttgtataaat ttcactttgt catagtttat aattctttta tatgttgcta gatatgattt 29101 gttagtattt tttaaggaat tttgcattta tacttatagt agttttattt ttctatgcta 29161 tttggactaa tttttgtatc aaggtaacac tggccccaca gaataaattg ggaagtgaat 29221 atttctcttt tttaaaaaag ctagtcaaga attaatatca attattcaat actaacaaat 29281 attgttataa attattaatt tctctaattt ttattttctt ccttctgctt gctttagttt 29341 tgctattttt tccagtgcct taatgtggaa ggtcatctta tctcatcctt tcatttgtct 29401 tttcattttc taaatagtgt ctttttagca tcaggtgagc tccccaggtt ggtagtactc 29461 catgtttatt gctgtacaac aatgacaggt aatatgtcct gaagacaatg gaaacttaac 29521 attcaaaatc ctcctagatt ccaccttata tgatatgtct cttcctttaa ttggtcctaa 29581 tttctaccct ttctctatta taaaccatga gtacaatggc attcaatgag ttctgtgagt 29641 ctttctagta aattcttgaa tctgagggtg ttcaggggaa acccctgaaa tggcagttgg 29701 tgtcagaagt gagaatcgtc ttatatggcc tcttcctttg aactttgcag ctggacccaa 29761 actctgcata atttgggcca gaagtctcgt gttgactttg cagcctaaag taccttgtag 29821 tttgtctaac cctcaataaa tttgctttca tcaaatattg tatttgttac cgcaaaatta 29881 ccatcatgtt ttttttctcc aaataactaa cattgggaga aatagccagc tgaatctgta 29941 actcaacaga aacaagtgat ccatatacca tataccatgt aagtggccat tttgcctcct 30001 tccaccacat cttagcaacc tcaaccattg ccatgagcca ctgtaggcct accggctaca 30061 aacaaacaag tatcttttaa aaacacttca tactcccatt tgataaattt cccagcaaag 30121 agatgtctac tttaactcta tgcaagtggc tcatattcac gaagtctgga gatattattc 30181 atgtagtgtg agaaaatcat cccagcgatg ccagcacatt ctccttccca taatctgctt 30241 agtttgcaaa catattcagg ccataggtga gagatttgta tttcacagta caacaatttt 30301 atggagggca ttgaaactta gattgagcat tttagtacag tcacacatca ctgaatgata 30361 gggatacgtt ctaacagatg catccatagg caatttcatc attttgcaaa cgtcagagag 30421 aatattacaa acacctagat tgtacagcct accacgtctg ggttatacgg tatagcctct 30481 ctctcctagg ctacaaacct gtgtactaca ttactgtact gaatactgca ggcaataaga 30541 acacagcggt aagagtttat gtatctaaac atacttaaaa catagaaaag catgtaaaaa 30601 tatgtattat aatctcatag gcccactttt gtatatgtaa tccatctttg actgaaatgt 30661 tattatgcat gacatgactc tatgacaaaa ataaaataac acactgtaaa aaattacata 30721 tgtatcaaac atattaatat aaaaataaaa atattcagtg taagaatttg taatgatcac 30781 aaaatgttca cagcttatat tttagtacag tttcaaatgc ctagtgcaat tactatttat 30841 ttgtgtattt taaacatgta tataataaat atttttcagg ttcaacaatg tatatcaatc 30901 caactggctt ttataaatat tagttaaaat caattagtaa attcatatat atatacacac 30961 acgtgtatca gtgtgtgtgc atgtatgtgt gtgtaaatgt aattgtatgt gtgtgtaaat 31021 gtaactggat gcatcctaat atttagcctt acctacaaga tttccaagat tcatttatta 31081 tctttagatg atgtgcactt aaagatttgc caaataaaac tgtaaccgtg gaaaatatca 31141 agatgttatt aaattcatct tgtgcacgta attgtttctc tacatttatg tttcttgcac 31201 aacttgcagt aatgctcatg cacaaaataa ttttctaaat aaaaaataaa aacattttct 31261 cagtcattaa ttcttaataa ttatttctct ctgataatta ttgtgaatta attcttaatt 31321 cttaattata gaataatgtt gcctttcaga gttctgaatc ttttgcatgt tgtatacatt 31381 tcactaacta gaacaacttc tggaatattg gcattaatta atgtcactca gcaattattg 31441 atttcaaaga aattaaatac cattcatatt ctgaatcaca agggtgcttt ggcatctaat 31501 ttaatcaagc tctttgtatc atcatctaca ctttaattac ttaacaaaca tttctctgtg 31561 tgagaaagat tgagcaggtt attgtgcttt gttaagatgc aacttttgct taatctagag 31621 ataggcaatg ctctctataa gggacaaaga gaaaaatgaa agagcaatag agacgtgaca 31681 ggcatggaaa aagacaatac atttataaaa caaataggac cacagatgac aataatgggg 31741 atcaaatctt gagatactga ctcagtttat aaccgcactg tataatagag caaatcactt 31801 gttaattttt ttaaaaatgg aatttaattt aagatgaata cagtgtttta aacaagacag 31861 gtcatcttaa aataaaatag tggaataaag tgataaaacc aatgtaaaaa tcataaacaa 31921 tttataaaga atttttgtca tgtaatttaa tatttttatt taaaaatcac caaaatcaga 31981 ataattttat cttaattaac ataatcatca gaagttaact aatttttact ttataatact 32041 acgtttaaaa atctttatat ttttaatcat atatgcttat atataaaata gacataggat 32101 atatatttaa tgttcccaat attatattgc aattgttcct atggatgtgg tttttcaata 32161 gaattaagta cttttaaaaa gtttcaatct caatgatata tatgtttgat ttttctttga 32221 caaagcatac atatattgat aggtaataat atgaaaatct tctaaagaca ttacaggaac 32281 atgaaaatgt aattaaatac tcactaattt gtaatgtttt atgtaagcgg aacacattta 32341 actgaaaatt gcttttatat aataaacgag actagaaaca ttttaactaa cggagtaagt 32401 cttcaaattg ataatctgaa ctatacaaga ggagaaactt caggcactca aatatttgaa 32461 atgatacaaa atatttatat aaactattat ttaacaattt ctgtttgtag agtgctataa 32521 tcaatataaa tgacatctca agtctttcta tcgctttgac cacatttacc tcctaatttt 32581 aattactaat atgttggagc aatgcataca actagattct gatcttcctt tttaatgagt 32641 aaaaaatatg tcctttgaga cagcattaaa gaaagagcac cttgtataaa ttcaatgcca 32701 agagacaaga tattcttgat tctgaagtct tgttctttta tacaacaatg taattaataa 32761 taagaagaaa agcaggacat agatgtggag tctattttaa tcaaaaattg tctatagatt 32821 ttgatgataa aatttaaaaa tctactatat ttagtcagtt acaaaaaact aggttgtggg 32881 aacatatttg gtcaataaaa cacccctacc aaatgctaac aagaaaaagt tatgtaccac 32941 ctttcttctc tgcagatggc ctgagatggg ttaatttgaa agaatgtttc caaacctgag 33001 gtgacccctg agaacagcat aatccactgc tgtctcccac attcagtttc tcagtttgtg 33061 ctcttttaat cttgggggga gggaagccag tcctttaaag caatcttcag catgatggca 33121 gagccaagga gtgtggacag gtggcacggt gtctgactta gttccagcag ccacttgggt 33181 ttctctgggt tttctctgcc ctagggatag caccactatt gaaaacatgt ctttgtgaca 33241 ttctctatgc caggaactcc caacacattt tccttgaaac tgatgaaatg aataaaaata 33301 aaccaagagg tgtgctgttt gtttctgctt cctcctttct gcagcccttc ttgatcatct 33361 aatattttta aatacattgt cgatcaccaa aaggagcata aggggtatat tgatttgtag 33421 ctgatgtatt aatagccgag cccctattcc ttacctgtag ctgctgggaa gaaaaccatt 33481 cttaacactc tacaaggtct catctccaga atttgcacct gtttctagct gaggactttc 33541 tctagcagca cgggagcttg atactgggca tgaagtggga agaaaaggtg agggttacta 33601 agaagaatct ccctggattc agtgatgtaa ttctgaggca tgttccacat agcttcccat 33661 agaattaagc ccagatatct aacacaggaa cttgcctgtt aacacgtgtg gtactggctt 33721 ttctatcttt cctgttttat tttattctct cttccttgtc tcactttcgc tgtgtcctca 33781 ctcctgcttt aagaataccc aaacaaatac attcatttat ttttttagac tctcagaaca 33841 cagttgatag ttgaacttgt aacctatgat aatcagcttg gatgctatac tgaaaggaag 33901 atggtgaact caccatgtct aattaagata aaatttaaaa aatatattga ttcatgtcca 33961 aagatttaaa aaacctaagc ggcagtgtca caatttcttc tttttagttt acatggtttc 34021 ttaaatgcct acaattattt taaaggaagc cttgggttta gagaaaattg agacatacgg 34081 aataaattac taacccattt ctccttgaaa tccattagat gctgatgatt tttcacatat 34141 acttctgaat tgaaaagcta gttgcgaatt atttttataa gcatatcctt atgtaatatt 34201 ttgtttttaa cagtaagttg aagatttaaa gattaaatta ttctatccag agaataattt 34261 aatctttaaa tcttcaattt actgttaaaa acaaaatatt acataagatt ttaaaacagg 34321 tcccatattc ttttgagtca attagaatat gtttgtatca gtctgtctac agttttacac 34381 ctgtcaaaat gtacttgaac tacaagtacc ttgaacaatt ttcacattta ttattcctct 34441 gaaaatgatt aaaagaatta gagtgaaatt ctgattggca taatttggga gagaaattat 34501 tccttggaga tcaacctctg ccaagatagt ttataatgac attgagactt tttgatttac 34561 aaagtttgtt atataaaaaa tactaagacg atgacagata atacacacac tttaattaaa 34621 attgtactaa aattaaatgt ctaaataaat tagaagggta cgtggtacat ctaattgtat 34681 gtttatatat ttcatttgtg tattttattc ctagggttgc ttttgcttta gtttgtaaca 34741 cgttcttatt tttatgataa tgtagtatat gctaaataaa gaaaaatcag gaaatagaaa 34801 atgaagaaga aaacattagc tattgtcaac caaataaaaa ttgtgcaatc tctaagcaca 34861 tgaactatgt attatttgta cagcatgtac aatgtttatg cttcacaggg tgaggtagag 34921 actgcaaaac attgaacctg ggacaaataa gaaagtaagg aaattttcac aatatattaa 34981 tattatagaa aatgttgaac ttaacagtta agatacaagt agtgaaaaat gatagtattt 35041 aaggagatct agaaaattta atctatatct gtaatgtgtg agaagtatta gaataatgct 35101 tgtatttctg gattggcatc gatttctatt gagactggaa acataataga aatgagggaa 35161 aaagaactta aattgtggat acttgagttt tatacctagg agtttgagaa atacattttg 35221 ttactatcaa agcagttggc acaagagtgt acaaaattcc ctaattgtgt caacgtggag 35281 aagacataga caaacagaga atagcaaaat agaaatagca aaaaagcaca aataaatttt 35341 acctgtattt ttacataaaa gccaattaga gtaggaaaac atgaaatttg tgtttaatca 35401 aaatttttct ctttcttata gtctagtgga ttatattact ggaaaaaaat tgaagcattg 35461 gtatgttcac aaaaaaaagt aaaatataag gtcaaaacca tgggaatgca gggagcagac 35521 aaaatatacc taaacaccga aactgatttt gccctacgga catgtaccaa aatgaatgag 35581 tgcagattcc tactgtcata catcacatag gacagtaaag aaatacatag tttttcctaa 35641 gatagggcat cacacaggag ctcctcccta aagctaggac caaagtttct atcctcagta 35701 taaagaagaa tcagaggtaa attagtccca tttcacattc cctggaaatg gcaaataaaa 35761 atgattgaga ttggacagat ttaaagaaat tcaatcatta atgatttaca gcaattaatt 35821 taaaaattgt ttaaatgtgc agtccaaaca tatgtccaaa cacctttagg ccaagaatta 35881 atataatgtg gtcccagaat ggtggtgcgt ttagtagact cacaaaaaaa ttcaaattct 35941 ctttggcaaa ttttcttctt actaatccgc aaaagtgcac aaaaataatt ttcagagaaa 36001 aataaatatt tgtcattcag aggcatctaa gtacacaagg aaatggtata ccaccgtttg 36061 aaaggaaagc agaaaaagag tacaaacaga tccacaaagg ttcattagta gaaatatcac 36121 tgttagatta taaagcacat ttgctttaaa aaattttttt taaaaaagaa tatattttag 36181 gagactaaaa aattgatgta gaaaatttgt aaagtagctt gtataaaaat atagtatttt 36241 aaattaaaaa ctcaaaaatg aactcatcag attagacatg gccatggtga gagttaataa 36301 atatttcaca atgcatcaca gaaaatttaa aaaaatgcaa aatgtggaca gaatcatgaa 36361 gagacaagga agataccgtg agaaagtgta gcatgtgttt agtgagtgtt ctcatagaag 36421 aagggaactg ggaagggaca atatgtgatg gtattttggc tgaaagttct ctagactttt 36481 gtaagacact aatccgcata ttgaaaaatt ccatgcatgc taagcaagct acaatggaga 36541 taaacctaca cctacgtatc tcctagagaa atagcaaaga atcaggaagg gaaaaatatt 36601 tcaattagca ctagaaaaat caaattacct ttaatcatat tgaaatcgga aagaatgaaa 36661 ggtaaaataa aaaatattat ttgttaataa taataatgcc attctgaaat tctcaaccaa 36721 gaaaaatatt catcaaccta tggctaaata acatatttag agagaaaaaa caaagcacca 36781 ccagcagaat tccactaaag aaactaaaaa gaaactctga aaacatgctt cagaaaggtt 36841 gaagttctga aatcaaagaa tgaatacaga gcaaaataaa catacaggta gatctaaata 36901 aaaaattagg tgttgaaaca aaaagatatt taaaattaga taagcactgc aatatgtatg 36961 ttaggaagca aattattagg gctgaagtat tcaatgaccc cttaattgtc tgacaagagc 37021 agaaaggtga gtatgacttt gcaacttttt tttttttttt tttttttttg aggaggagtc 37081 tcactctttc acccaggctg gaatgcggtg gtgccatctc cgctcactgc aacctctgcc 37141 tcccaggttc cagcaattct cctgcctcgg cctcctgagt agcggggatt acagccgcgt 37201 gccaccatgc ctggctaatt ttcgtatttt tagtagagac ggggtttcac catgttggtc 37261 aggctagttt ccaactcctg acctcgtgat ccacacgcct cggcctgccg aagtattgag 37321 attacaggcg tgagccactg cgcgcgaccg attttggaac tttaataaat tcagtggaca 37381 ttatgcattt ctctgttgta tctatgaaaa caataaaaat aaaagtcata atttaaaaac 37441 aagaagacag aaactgatag gagaaaatga cacattatat acatatatat atacaacaaa 37501 ttaataaaac aaattacgta taaatgatca aagattaact taaacctaag tagacaatgt 37561 ttttgttaaa atacaaagat tggcaaaatt aaaaaaatcc gtctctatca tagttacaag 37621 acaggcaact aatatataaa tttacagaaa ctttgaagtt caaacaatac agatactgtg 37681 tatatatgat atacatacaa acatactaca tgaatataat tttttaaaaa gttgctatgt 37741 agacaaaata gaatgtaagt tagaaacatt tattaaaata agttagtcta accagtgtga 37801 taaaagtttt aagttattaa gaagatgtga tgacttaaat gtgcattagc ctgatacata 37861 tatacatata tacacacaca ccacacacac acacacacac acacacgtat ttagatagtc 37921 aaattatata aagcaaaaat atcagaaagt aagtagaaat ggataagccc ccaaatcatt 37981 agacatttca aacacacatc tttcagtaat agataaaaga aaaaattaaa agagtaagtt 38041 ttaaaagaag ctagtggatt ttaaaaaggg caaatgttat ataaggaaca tgaatattat 38101 aattcatgtt attttcatgt tcatacagaa tacttacaaa aattaacatt ttctagacca 38161 taccacaaat tcaaacaatt ttcacggaaa taacgtgaca cagaatatat ttcctaaaca 38221 aacagcaatg aaggtagata tcaatacaaa aaagaaagct agaaacataa gtctaataat 38281 attggttgga agctgtttta attaatattg aaatatttta aaggtgaata gtcaacacaa 38341 atgaaccaaa cacttttgta aggccactaa gatgcatgtg taatgtgtaa tgcctccttt 38401 tataaggagt aaatctgtaa catcacctgg gctatttgac aactgcaaag tgaatgtgag 38461 aaggagagaa acagtgagag agagagagag ataaaaccag taaaataaac ataaagaatg 38521 aaggagatag ccgggcgcca tggctcatgc ctgtaatccc agcactttgg gaggccaagg 38581 caggtggatc acctgaggtc aggagttcga gaccagcctg gtccaacatg gtgaaaccca 38641 ctctctacta aatatacaaa aattagcctg gcatggtggc atgcacctgt aatcccagct 38701 actcagaggc tgaggtggga gaattgtttg aacgtggggg gtggaggttg cagtgagtag 38761 agatcacgcg actgcactcc agcttgggcg acagagcaag agtccgtgtc aaaaaaaaaa 38821 aaaaaaaaaa aaggaggaaa tagtacatga aaaagcagaa ttaaagcaac tgagtatata 38881 tttaaaaatg caacagctca ctttttcaga aaaatattaa aatattaaat ctaacaaata 38941 tctaggtaga ctgatggaga aaaatacaga aaatgcacaa aaaaccaatt acctggaatt 39001 caaaggttac aaaacgtaag cagttgtagg ttttaaataa gcaatgactt tgagttcaac 39061 catgatgggg tatattgaaa agaatctctc agaaaaaaag aaaaactgtt ataaagctat 39121 gtagaaaatg ttaagcacta ttaaagtctt ccaattctac cagttatgga gttattggtc 39181 ttggactaac tctcctgaaa agaaaaaaaa caaaacaaaa cctaaaaacc tggataaaat 39241 ggcctaccgt gggcactggc aatgcaacca agcaggtagg acatgggtgc tactttctct 39301 ttgtcagaac acaaagcatt catacactct tctcaccctc actctcacct tttaatctta 39361 gatctactat taaatgtatt caactactat caatcctttg gtcaaaattt cttttctcac 39421 attttgcttg atgcacttgg atagactgtt caagaaagtg tgagtactga attcctcaaa 39481 ctcttgcata tttaaaatta catttttgaa ccttgatgct tgaagtgtag cttgggtaac 39541 aggtgggctt taagccgatt ttggcatgca aggggttgag tttattaggc atcagcacct 39601 ctgaaaatcg tggggatgca ggcttaattt caacactatt ctaaatactt gaaagatata 39661 taattcctta ataaactcct ttgtctacaa atggttcaca ttaactcaat atccatgatt 39721 aaacatctat aaaatcaagg cactgttatt tagtggagac ttgctggcta ttctatgaga 39781 ggaggtattg ttattttaat ctcatcctct cataaaagtg tatcatatta ctcataacca 39841 gcccttcata ttctattcct attttggtat tttaaaataa gatatctttg aaactcttga 39901 attcaaatag agaatctgaa tagtttttaa aatgtcaatg aaatgccatt tcttcatgct 39961 tcaacaacta aaatttgact aaagtgcttc tcttcaaact ttctgtaaca ttttttaatc 40021 taaattctaa gaacgatcac aataggtttc aaccacaaat gtgagaatat tgtaaatgtt 40081 cgggtggaaa aatttttaaa ataattttgt agtaattttt gaatcatagt gacagtgcgc 40141 taaatttttt taagtcaaat attactgtag acatttaagt caagattcta agaaactgtt 40201 ctaaagtcca aaatttagtt tcatatacaa tgatattata tatatatttg catataaaat 40261 taatatatgt gagccatgtt tcaaatagtt gagagattat atcaaagatt cttgattata 40321 taaaatgcca attacttata ggcacacgtg ctttaaataa ttacaaaggc agctgtggtt 40381 gattctactc ttgctactgg catttatatg gacatactat tatggtctga agaatattta 40441 ggcaaattta tccctcatac gatcagaaga acaatgcacg atagtttata tctgaaagga 40501 aaaaaaatct ttatatggtt ctgaaagcct aaatcattaa caacttggat aataattagc 40561 ataaaaatac acaaacatgc cctcttccta gcggtaagta cagagtgaca acagaatcaa 40621 agcatgtggc tatgtgcatg tttatatttc aagacgcaga gcactctatt cctcttctct 40681 gccctttcta gatggcacaa ttcctcatga atctaagtgc tgtcataggg tggattaggg 40741 tgacctgcca tttgtatgca accgatctct attttggaag taattaatgt aaaaatatat 40801 ttttaaaaga taatttcaaa tttcagggca aactagcatg gtttcacccc tttcctttgt 40861 aacatttttc ctaaggttgg aaaagtaagg taggctttag tacgattttt aataacaagt 40921 tttcaaagtg agacgcaaaa tggtggcgcc aacacatttc aagtctgcta cattttgaat 40981 acacttattg gagaaaagac cttctcatca tttttctctt acaggaaagg aaataacatg 41041 tacagttgac ccttaagcaa caccgaggtt ggggtgctgg cccccctgca cagtagaaaa 41101 tccactaaaa ctttgactcc tccaaaactt aactactaat agcctactgt aagccttaca 41161 aataacacaa gcagtcaatt aacacatatt taatgttata tgtcttatat actgtattct 41221 taacaaacac gccagagaaa agaaaaagaa aatcataagg aaaatatatt tactagttat 41281 taaatggaag tagatgatca aacaggtctt catcctcatc cttttcatgg gcagggtgtg 41341 gaaaaggatg tagaattttt ggttttgcta agtggacccg cacaattcaa acccctgtgg 41401 tgcaaaggcc aactgtatag ccactgaata gcaatttatt tctagaaatt aacctcacta 41461 aaatattctt agaaagatgc caagaaaaaa atgaataagt atttttggta catctatttc 41521 atcatttcat ttcctcattt catcatttca tttcatcatt tcatttcatc atttcatcat 41581 ttcatcattt catttcatca tttcatctca acatttcatt tcatcatttc acttcatctc 41641 atcatttcat catttcattt catgatttca tctcatttca tcacttcatt tcttcatttc 41701 atttcatctg aacatttcat ttcatcattt cacttcatct catcttttca tcatttcatc 41761 tcatttcatc tcatcatttc atctcatctc atttcatctt ttcatctcgt catttcattt 41821 cgtcatttca tcttttcatc ccatttcatc atttcatcaa ttcaacattt caattatttc 41881 atcatttcat catttgactt catcatttca taacatttca tttcataatt tcatcttttc 41941 ttttcatcat ttcactttgt catttcattt tgtcatttca tttcctcatt tatcatttaa 42001 tttcatcctt tcatcatttt atctcatttc atcctttcat ttcattattt catcatttca 42061 tctcatcatt gcattttgtc atttcatttc atttcaacat ttcacttcat cttatcattt 42121 catctcatga tttcatttca tctcatcatt tcatttcgtc ttttcatctc atttcatcat 42181 ttcatctttt catctcattt catttgatca tttcatcaat tcatcatttc atcgtttcat 42241 tatttcatca tttaatcatt tcacttcatt tcatcatttc atcatttcat atcatttctt 42301 catttcatca tttgatcttt tcatttcatt tcaccatttc atgatttcat ttcatttcac 42361 ttcatcattt catttcattt caccatttca tcattccatc atttcatttc accatttcat 42421 ttcatcattt catttcatcc tttcattatt tcattgcatc atttcatctc ataatttcat 42481 tatttcactt catctcatca tttcatcatt tcatctcacg atttcatttc atctcatcat 42541 ttcatcacat ttcatctcat caattcatct tttcatctca tttcattatt tcatcctttc 42601 atctcatcat tcatcatttc attttatcaa ttcatcattt catttcatat ttcatcattt 42661 catttcattt catcatttca tcatttcact tcatcatttc attccatcat ttcacatttc 42721 ttcatttcat atcatttcat catttcactt catcatttca tttcctcatt tcatttcacc 42781 atttcatcaa ttcatttaat catttcatct catttcattt catcatttca cttcatctct 42841 tcatttcatc tcatgatttc atctcatcat ttcatctttt catctcattt catttaatca 42901 tttcgtttca tttcaccatt tcatctcgtc atttcatttc atttcatcaa ttcatcattt 42961 catttcatta tttcatcatt acacttcatc atttcatttc atcattgcat atcatttctt 43021 catttcatca tttcatcttt tcatttcacc atttcacttc atcatttcat ttcctcattt 43081 catttcacca tttcatttca ccatttcagt tcatcatttc atttcatcac tccatttcat 43141 catttcatca ttttctttca tctcatttca tcatttcttc atttcatcat tttatttcat 43201 catttcattt aatttcagtg atacatgtat tcaagtgcta atgtgatgcc caggagacac 43261 cctatttccc tttgtaaaac acctccttca acaaaaggca acctctcatg gctggctaag 43321 tctacaggga taccagcctc tcttcaacca cccaatttga tttagaacct caaacagcac 43381 ctcagtttca taaaaaccta aaacataaaa cacaacactt ggttgtaagt gagccaacag 43441 tttgtctctt tctctgccca aggcttaagg ccgtgtttcc ccaactacgt tcagtggaag 43501 aaaagatccc ctggacaaat aagtttgaga actgttgttg caggacttct cagaaccttt 43561 aaaacacaaa tcctcatccg gagggatctt caggagggag atgtctgatg cagcacaact 43621 ttctttcaca ggagcatcct gcagaataca gtatgagatg cagaaaggct gcaatgagtc 43681 tttttaatgg cccgggcctt ggtgggggtg gggtaggagc tctccagata gcatctaatg 43741 agtaggaaca ttcaggttgc tttttttttt ccttattggc aaacctgtgt gcacaccatg 43801 aatgaagctg atctccctta tccatatcaa aactaaaccc aaattaattg gctaaattgg 43861 gaatcaacac ctccaggagc tacgcagaag aaagccccac cacactttaa agtagcttac 43921 ctcatatttg acgaaagcaa aacacttatg accagtgtgc tgctaataca agtctacaga 43981 taacgctgca tgaaaaatta gttttcccaa tcgtagctgg catagtccac attttgcatt 44041 acactttccc cccttgtttt aaattttaaa cacaggtctt tttctcttct ttttttaaat 44101 tttaatttaa ttatacaaga cagagtctca gtatgttgcc caggctggtc ttgcactcct 44161 gagctcaagc gatacatccg tctccgcctc ccaaagtgct gagattacag gcctaagaca 44221 ctgtgcccgg ccttaaacac aaatcttaat tcattcttac agttatcctg aggttagaaa 44281 aatggaaggg gaagaaaaat ggcaagcagg taggttgact tcggcttcat tatttgaaag 44341 gacagtttgc tcagttaaaa cacactactg cccacaaagg ccaagacaac agaaaaatac 44401 agacatataa atagatttta tatgtgacag cagtttcaat ggagactttt tcaatgcaaa 44461 tgacaaacag ctgtgcttgg gaataaatga caaggaattt tttttatctc aacagctgtc 44521 ctgagagcac atctctacat ctctacctat attctggaat cagggagaaa gccaaaacgg 44581 atgacaagat actagatcag ccgtgtccaa cccttttagt acaaggactt ttccgcctat 44641 ctgtggtggt gggtatcatg aaaattatgc acaaaccttt tttttttttt tttaagctca 44701 tcagctgtcg ttagcattag tgtattttat gtgtggccca ggagcattct tcttccaata 44761 tgaccccgag aagccaaaag actggacacc tgtgcactag atcaaaaggc tactccttct 44821 ggaagcaatt ataaagaatt tctgacatta tcttgacatg aaaaccaatg gatagtggga 44881 cagaatgcaa aatcttcaag aatttttctt gttggttttt tttttttttt ttttttgagt 44941 caaggtcttt ctctgtggcc caggctggag tacactggtg agatcacagc tcagtgcaga 45001 ctcaagtgct cctcccacct cagccacagt agtagctggg actacagatg cgcacaacca 45061 cccctggcta atattttatt ttttgtagag atggggtctc actatatagt ccaggttggt 45121 ctcaaactcc ttgactcaag ggatccagga caggataaca ggtgtgagga gccaccacac 45181 ctggccatgt gcatgaactt ttaagacaaa cacaaggccc cacaaaagtt aaggttttcc 45241 cacctaattt ccaggggatc ttttggtgca aagctgagaa gcccttaaaa gtacacagac 45301 aactccaaag attcaagaga gttcattcgg ggtgagccag cccactgggc agactgacct 45361 tcaaaaaagg cccacccatg acacacacca gatggctctc caagaatctc ttcagtcctc 45421 agggtcccta aggcactgga cagagctagg aaagcaaacc catttgcttc tccctgcagg 45481 aaaccccttg aggtcaagac cccacaatca gacaaggatg gagtggctca ccttcagtca 45541 acaggccaga ctcaaggtgg tataatgtct taaccaaggg tgcagtcctc caggtctgac 45601 tcccaactca gttctccttt aataaccaca ctttgttaat tctccttaac aggagttcct 45661 gacaagtcag ttctccctca gaccttcagt ggcctcacct agaagatgag agggctggat 45721 cagatggaaa ttcggggagt aagggaatgt cggcacgcag cccacctccc ccaagggacc 45781 ctggagcctc catcccagtt cccaccatgc acccgcccca caaatcctgc ccaaggtgag 45841 ggctggtccc gggtcctccg ggtgccgcaa cagcgaggga aggagggagg ggaagcctcc 45901 aagggcgcga cgcaggctca aggatgcaac tcggccagga gtgaactggg gacccgaggg 45961 aggtatccgg gctgctcctc gagcccagcc cgggtccccg aaccccttac ctccagggtc 46021 cgtatctcct gctgggtgag gccgttggac acagcgcact tggtgcgcag cccgtgcagg 46081 ctgccgatgg agatgccgat gagcttctgt agctgcccgc actgctgcag cgtccggctg 46141 gccgcggccc ctgcgccacc ccatcacccc cgcccccgcc ctccttcttc tctcccatag 46201 cctccccgcg cagcgccgct ctatgcaggc cacagtggcc aaggcgggga gcccggggcg 46261 cgggcgccta ggcaaggaac cccggagacg ggagagctgg accaggagcg cccctcggcg 46321 gtgcccttac caggacgcca gtagagctgg cagccgagtc tgccgctccc gccctcagaa 46381 ccgcggcggc ggggacaaaa agccgcggcg gcgggggcaa aaaggcacgg tggctggggc 46441 aaaaagctgc aaaaagcacg gctgcggggg caaaaagcag caaaaagccg cggcggcggg 46501 gggaaaaagc cgcgggggca aaaagcagcg ggagcggggg caaaaaacca cagaaagccg 46561 aggcggcgag gggaaagagc cgcggcggca gggggcaaaa agctgcaaaa agcagcggcg 46621 gcaaaaagcc gcggcggcgg gggcaaaaaa accgcggcgg cgggaggcaa aaagccgcgg 46681 cggcggcggg ggcaaaaagc tgcaaaaagc cgcggcggcg gggacaaaaa gctagggcgg 46741 caaaaagccg cgctaacggg ggtaaaaagc cgcggcgaca aaaagccgct gagagggggc 46801 aaaaagcagc gggagcgggg gcaaaacaca aaaagccacg gcggcggggg caaaaagctg 46861 caaaaagccg cggcggcggg ggcaaagagc ctcggcggca aaaaccagcg gcggcggcgg 46921 gcgcgaaaag gcgcaaaaag ccgcggcggc gggggcgaaa agccgcaaaa agcagcggcg 46981 gcggaggcaa aaagccgcgg cggccggggc ggaaagccgc aaaaagccgc ggcggggcag 47041 gggcaaaata ggagaaatga ggtaggaggc cagcacaact tggcattgct ggagtgtgat 47101 gtgataggaa aagtgcagcc aaagacaaag aaagatgtaa gttggcttga ctcagtgcag 47161 ctaagaaccc agatgttatc ttgagggtat taactaataa gcagtttaaa tcagaatggc 47221 acattctgat ttgtttttta tattcacatt tggcaggcat agatactgtt tgaagagagt 47281 aaagtcagta gatagaggta acaaacttaa atatgtgcca agtctagaaa caagagacta 47341 gggggataag gacctttcaa aagaaaatgc aagatttgaa aactgattgg ctgggggatg 47401 aggaaaaggc acgtctttaa ggtcaatccc tgttttgctt taagttgtta gggggtggtt 47461 ttatcacata ttgtagaata tgtcatttca gttttgaaca tcttgagtta aattgtccta 47521 acatatttta tgaatttgat tttcttccct gggaagctag tatttcaaaa acttaaagag 47581 tatagatttc caacttgtat ccaatttata aaactatctc taggctgctg gtttcaggag 47641 gaggctcatg aatattctat ttgcagagaa tatatcagga gttaacaaca gcgtcagtat 47701 ttgtggacga ccagttaact aagccacctc ttagtgtatt tagataggaa atcttagctg 47761 aagatattca ataatgaacc aacagtgact aaaaaattca atatttaagt atatttcatt 47821 gcaattaatt tgaatttaag tagccatata cagctagtat ttactacatt gaaaaatgca 47881 aacaagagga aaaaattaat aaccatccct aataccacat gccaaaatcc tcatcaattt 47941 attctagcta aaggagttga tcagaagcac caatttaaag caccaatcac tgtcgttctc 48001 tcagaaccat ctcttctctg aacaaaacaa gtagaagagt taatagtgaa tctgcatttt 48061 ccttgcctat tttaaggttt tgatgttgac actaatttgt gaaatccctc ctgtggtgtg 48121 atatttcgtt ttccttgctt tttgttagga caagaatgct tcagctctta atttaaaatt 48181 atgtttctcc ctcccaggtg gagtgaactt agcatgcatt ctctgacata tccaagtttt 48241 tgttaatatg aatttggggg gaaaagcata cttaattagc taagacttct tattctaggc 48301 ttgaccctgt gttcgacatc tttttaattt gtagttgcat aggctgctct ctgacactgg 48361 ttagtgatct ggaagctata ttaacgttag gagaggtggt gtatgagcac tagaggtatc 48421 cttgcaaggg aagacttgtc ttatgtcaat acgtcttttt tttgcacaca agaaagtcaa 48481 tgtttgagtc ttctaaaatc ttcctatttc caagttgcag agtacaattg attcctaaac 48541 aacgatctaa tttttgactc agagacgtgg caaggtagtg aatcaccatt ataatttaac 48601 aatcttcaag ataaaattat ttctctgata tttagatttt gcccaattat taagatattt 48661 gggtgtttcg ttaagaatgg aagactctag tctcttgagc agagactata aaggcctcag 48721 atgatcattt ataattttat gctcttttct ttaacacctt caacacagtt ggaagcagcc 48781 aatattcccc agtgttgttg tgttttttaa accaaatgca tggttcagtg gtagaaaact 48841 gggctgatcc aagctgtttt cagtaaacac ttcatttcag gtgacctatt tcatattaaa 48901 taatctctag atcctgtctt caaaactaac tagatcagat aacctaccct agattttccc 48961 ctttagggtc tgttagctgc agtcactttt gtgaaaatga ttgcgatgaa aagatagagt 49021 tgtagatggg gaaaatgttt tgactaattt aagcatagtg gtatttaata tgagaattta 49081 agttacacac atttgaaaat tataatggag tctcttggct gagctttaaa aaaaatagcg 49141 tttaggctaa aaagggaact gctacctctc ctaaaatcag aaagatgtta cagtaattct 49201 ccattctcta gaattatcag gaagcacctt tgtgatgatt tacttttgct cttgggagtg 49261 tgagcctgtg tagtcgtgga accgtcaatt agagtgatgg ctttctgatc ccaaagtcat 49321 tcgttctgaa aacaatattt ttcataaatt tgaatgtgag aagttttgat cttgccattc 49381 ccaagtaact ctcttaataa gaggcatcag catgcttcag tgacagctgt caccttccag 49441 tgctgagagt catctttgag ttctccattt cactccctac actccaattt agctgcagtt 49501 ctcttggcca gtcctatgaa atacatccat ggcctaacga cttctcacca ctaataccac 49561 tcatacttac agcattctca cctaagtcac tacctttttt ctctggatta caatagcctc 49621 ccaatttatt tgctcacata acctatttat tctacacagt gcaccagata cacccctttg 49681 aaatgcaaac ggaatcatat tattctctgg tgaaattatc tcatatattc ctatcgcatt 49741 taaaattaat tcagaataat cccatgatta tcaaaaccct atgtgctctt ccacaacatg 49801 atttacttcc aagatatctc ttcttcaact tttttttcac tgtactgaat tggtgactaa 49861 aagtcatatt tttgtttttg cttaaaaagt cttgacttgt aaatttttca gtttctcctt 49921 tatccacagg taactctttc ctcataaggc gaattgcttg cttccttgag ttctgctctc 49981 aaagataccc ttcatgttct acctaatatt aataacttta atcattcatt attccattac 50041 tatgctctat agtgtataca atttctgttc tttgtcctgt tattaactaa attatttatt 50101 tgttccagta acgtattcca taaatattgt acacataaaa attatgttat ttttattgct 50161 gtatgctcag ctgcccaata acagtttgag gattaacata tttgttaaat gcacaaatac 50221 attctttcac aaatatttaa taattttata ttaaactccc tatatactta cagtatgaat 50281 tagataattc agaataaaca ttccattgga aaaaactaaa caatttgtta taaaacatcc 50341 ttaaaagcat cagaaggtta atacagacat gaagaattac aggaccaaat taagaacggt 50401 atggaagcct gtttgtgagg cttatgtttg ggttatctct ttacttagag tgactataaa 50461 tctcaaaaga gaactaaagg gagaaataac catatctact aacatggtaa gggtatttaa 50521 acatctctta gtaattgaga aaattgaaag aaaagaaaaa agaaagggag aaagagaaac 50581 agagcaaaag ggataatgaa ggagagaaag aagaagagaa aggaagagga agaaaagtaa 50641 aaaggaggag gagggggagg gaggaagaaa gaaaggtgaa aggaaagaaa ggtaaagttt 50701 ttaacagcat aatttatcct tgtagaatat gaatgttggt ctatttgatg atgtcccaca 50761 gattccttag tctctgctca ttttttatct gtttctcaga atcaatattt tccattttct 50821 tatcttcaag ctcatgactt tttctgtgtg tgcaaatata ctcttaaatc cctctggtga 50881 tttttaaatt tttatcattg tagttttcca ctccagaatt tctgttatct ctttgttgat 50941 attcctactt tttaatattt ttttctgatt ccttcatttc tttgtttatg ttttcctttt 51001 gacatttgac atttgagtat aattaagaga gttgttttaa agtctttgtc tagtaagttt 51061 gatgtctggg tttccttaga gatattttct gtcaatttat tttgtccctt tgaatgaccc 51121 atactttccc gttctttgta tgccttgtaa ctttttttga aaactggaca ttataataat 51181 tataattact atgtggttac tctgtaaatc agaccccccc ctacaaacat actaacgttc 51241 tgtggtttta aattttattt acttattata ttgttaagga ttttttttta gtgaaatttt 51301 ccaaagtgat taacaaaact gtttgcttta taaggtgtgg tcacccaagt ctttttgttt 51361 ccttaacaaa tgttaagata atgttttgac tgattttctt gtatgtcagg aactaagcaa 51421 acaggcaaat acaacaaaaa caaaaagaaa aacaagtaat cattatccag caaaataggt 51481 ctctaggcca tgcagactgg ctttgtgctg ggttctttaa agccgggaca aagtgtgtgt 51541 tcactcttgc actgagtgaa gttcaagttc actcttgcac agagcctgca ctgaggggag 51601 ggatcagcga aggtaaaagt gtagggtctt cttatgacat ttgtcagcat gtggcttaac 51661 gtatgcatac atgtgacttt ctagactctc ccatgtacgt gaatgatttt gaatgtctta 51721 gttttccata tactctactc caacttttct tcctgtgctg aaggtgatct actatatgtg 51781 taaactctaa tttttgccct aagcatctgt ggcttgttag gtctccttgt agagtttctt 51841 aataatgtcc attccttatc tgttctgtat cctagcaaca cacacaaaaa agcctttcat 51901 tagtccttta ggtatccccc agaccagtca gaacagacac ataataattt gagggtaaga 51961 tcttctcttg ttcctttgga cgatggacca ggtttcctca ctgggaacgt gggcttctga 52021 cacttcaaaa cagccaattt gctggggcaa aggcaagtta aaaacgtcat aaagttttca 52081 agttgtcttg ttcttgagtc tgctttcact tggttgttgt aatcttttga ccattttcca 52141 gagttttggc aaagtttatt cggacagttt ctcttagttg tgtgatgttt ctgtggggaa 52201 gtgaaagatt gcagttgtct ccactgccat tttgctgatg ctcctctttt gtcaattttt 52261 gcttcatgtt cttatgcttt gttattagtt catgtattag ttttctaggg ctgccataac 52321 caagtaacac aaactgggtg ccttgaacaa cacaaattta tagtcttata gtcctggaag 52381 ctaaaagtct gagactgagg tgtcagcagg gatggtccct tcaagggcta tgagagaaag 52441 tctgttctgt gccttgtttc tagcttctgg tggtttagtg gcagtctttg gcatttcttg 52501 gctaatctct gccctcataa tcacatggta ctctccctgt atgtatgtct ccctctactc 52561 aattttcttc tttttataag gacatcagtc atattgaatt caggctcatc tgattttatc 52621 ttaacttaat cacctgcaaa gaacctattt cctaatgagg tcatattcag tggttaggat 52681 ttcagcgtct atatagatga aacaatttag ctcatatttg tgcatacatg attgtaatag 52741 ctatgtcttc caaaagtgct gaccccctta ttactacaat ataaattttt aaaatcctat 52801 tcacattttt aatagtctat atcgtgtgtt atgagtataa tgagttcagt gttcttatga 52861 ttgctctttg catgatattt tttgtcatct ttttactttc aatccattag tatccttgcg 52921 tctcagcgta tattgggatc acttgtttta atccagtctg agaatctctg cctcttgaat 52981 ggattttaat ctgctcacat ttaatattat aattggtata attctattta tgtctgccat 53041 tttaccgttt gttttgtgta tttctcaaat atttttcttt attgctttat tttgcaatga 53101 atgaatattt tctaaaatat ggaactttag attactaatg aattatttta gtatatattt 53161 ttgggaattt ttgttgttgt tgtaagttta ccatataggt atatggaaaa ttaattattc 53221 aaatcatctt ccaatttata ctagtaaact tttagtaata catagaaaca tcattcttat 53281 acaaatctct tatatttcct ccattttaaa gtattatcac tttacacatt atatctatta 53341 aagttacaaa gccaacaata cattttagta attactactt taccatctag agtgattacc 53401 ttatcacaat acatttttct tccaactacc tcctctttga tgttactgga aaatatgtta 53461 tagatatatt acatttctac atgtcaaata ctcagcaata cattatgagc atattattat 53521 tattattatt atcattaaga cggagtctcc ctctgtcacc caggctggag tgcagtggca 53581 caatctctgc tcactgcaag ctccatctcc tggcttcatg acattcttct gctttagcct 53641 ccggagtagc tgggactaca ggcacctgcc atcacgtcca gctaattttt tgtattttta 53701 gtagagacag ggtttcactg tgtcagccag gatggtctct atctcctggc ctcgtaatac 53761 gcccacgtcg gcctcccaaa gtgctgagat tacaggtgtg agccatcctg cctggccatt 53821 atacgcatat tattttataa acaatttatg ataaagagaa aacatggatt tctactgtct 53881 tttataatgt taatattacc tataccagtg cttttttaaa aatgtggatt caaacgactg 53941 gcttgtgtaa cttgctttta gccttaggaa tttattttag tgtttttttt tttttttttt 54001 tttttttttt ttttttttgt atggtaggtc tgccagcaac accttcagtt aatatttctg 54061 tttatctggg taagactttg tgttatcttc atttttgaaa aataattgct ggataaggaa 54121 ttggtggctg acagtttttt ttcctttgca tcttttgaat atattattct actgcctctt 54181 gccttccatt gtttctgtta agtcagctgt taatcttaca aaacctaggt gttcaaaaaa 54241 taaacatgtg catgaatatt tatagcagta atattcatac cgtcaaaaag tggaaacaat 54301 ccatatgctt gtttactcat aaatagacac ccaattttca gctataacaa agaatgaagt 54361 acttatacat ggtataatat gggcgaaatt tgaaagcatt atgttaagtg cacaagagga 54421 caaatattac ttgattttat tcacatgaaa caccaggaat tggcaaatta attgggatat 54481 aaatcagatt agtggtcatt agggctcagg gaagcagaat agggtgtaac aactttatgc 54541 ataatgggtt tttagaaggg acatgacgaa attttcctgg aacattgtga atatactaaa 54601 agcaagtgca ttgtgcattg tatgctttaa aatggttgtt attaatttta tattatgtga 54661 ttttttacct taaaaaacaa aaaagagaaa atagccttac tctatataca ataaattcaa 54721 gatgtgttac aaatttatat gtgaaatcca aaatagtata atatttaagg aatagctgag 54781 tagaataaca ctaaaattta acataatgaa atatttcctt aaaaaagaaa aaagcacagt 54841 aattaaaaag ggaaatatag ttaatatttt ttctctccat taagcatgcc attaactgag 54901 taaaatatca agctgcaata tgtaaactgc attttctaaa accataaaga aaataagaaa 54961 tgaaaaggga ttggggaaaa aaatccaaag gtacagtcaa ctacacaaaa aaaccttagt 55021 ctcattaatc agtatgaaaa tgcaaattgt aactgaaata agataaaact acaattcaaa 55081 gagaaagcct aaaatttcaa ccccccaaaa attctgggtt ttggagagct gggatggaat 55141 agggctgcta accttacaac aatgaaagaa ccaaactaac ttcaaagtca tgactttatt 55201 tttatagtaa ccaggttgcg aagaactgag taaaaatgtg agggaaaaca agcaactgca 55261 aggagaaaga ggacagatgc acttacatag gacagatgca aatagacacc actatgacaa 55321 gtaaagctgg aataatcaat aaattcctaa agacaaagtg gggctggtca gattgggaga 55381 ccgctgacag ctgcagaagt tgggaaagat ccatcatctt gaaaactttt tccccacaaa 55441 cccactgtga tctctcaagc aattggtaag gaatccaaga cagtctgtat atgatacaga 55501 tcagggagag cagaacactt gggaggtgac caggtcttgg gggccgagcc cttatgaatg 55561 ggattagtgc ctttataaaa gaagctcaat ggagttcttg tgtgccttcc actatgtgag 55621 gacatagaaa gaaggcacca tctatgaacc atgaaatggg ctctcatcaa cactgaattt 55681 gtgagcatct tgacctgaga acttacagcc tcaagaagtg cgaaaaaaga aatatctgtt 55741 gctttttagt cacctggttt atgttatttt gttataagag tccaaataga ccaagatatt 55801 ccattccact taatatgtag gggaagacaa caaaaactgc cacacttaga atactcctga 55861 tgctgggagt atgaaaacag gaaaaacaaa acaaaactgc tcttgaaggt gaaggaggaa 55921 tatcactgag ctcaccaaca cagcaggaaa agaacagtga gaaggctaca ttcatgagac 55981 cctgagaaaa agtacctgca taagactgag atgaaattac ctaccctagt tataattgaa 56041 atcccaaaaa gaaaagagga aaaaataatg gagcaaaaga aatatttttc aaaataactg 56101 ccaaaaatat tctaaaagaa gtgacagaaa atcaaacttc agatatagga aactcagaga 56161 atgtcaaata gaacaaaaat aagaattaca tcttgaaaaa tctttaaaaa atcaactcta 56221 aattttatat cttgctccaa atatatagag atataaatag gttatcatcg agatatggag 56281 aaagccatgt catggaaaca ataaaataaa gctgtggaag ggctacattg atattagaca 56341 caacagagtt cagaacaaga aatagtatca gagttgagaa gtaataagta atataataat 56401 caattcttaa gaagatgtga acatcctact aattagggta tgcagctaac aacagaacct 56461 ccaaatacat gaggtaaaac aggaaagaaa tcaaaggtga actagaaaaa tccaaaatta 56521 tatttgcaga cttcaacact tttgtcttag taatggacag actaggcaaa aactcagtaa 56581 tcatatggaa gataagaaca acaatatcac caacaagaca tccaatcttc aatggcagat 56641 actctttcct ttcaagtgaa aaaaaaaaaa aaaacaacaa cagtatggca tattctctaa 56701 caaacccaga atttctaata tttgcggtct tccttccttc tttccatctt cctttctctt 56761 ctcttccctt cccttgcctt cttccttcct ttcttctttt cctctttctt ttctctctgg 56821 ttttctttct tttctttctt ttttctcctt ccttccttct ctccttcttt ctttcctcat 56881 tctttcttcc ctccatcctc ccttcctttc tccctccctt cttttcttcc ttttctctta 56941 ttctttcttt ctcactttct tgctttcttt ccttttttct cccttccttc atcccacctt 57001 ttcttccttc atccctccct ttctttcctc ctttttcctt ccttacttcc ttctttactt 57061 ccttccttct cctctttatt ttctttgttt cttgcctttt tctcttttaa cattctctct 57121 tcctcctttc cttcctccct tcctccttcc tttctttatt ctttctttct tgtttctttc 57181 tttctttctt tctttctttc tttctttctt tctttctttc tttctttctt tctttctctg 57241 tctctctttc cttcttgtgt tcttgctttc ttttttctcc cttcctgcct ttctcccttc 57301 ctccctccct cccttccttc tctgatttcc tccttctttt ctttcttctt tctttctttc 57361 cttcctttgt tctttccttt cttctttttt ctttcttctt ttcttttctt tctttctctt 57421 tactacaatt catattattt aaaaaattta agagagggag gcagaaaaat aaagaacact 57481 ttaatctgca ggtaaataga ttatgtctgc tgtatacaaa agaatggcct cccaaaaatg 57541 ttcatgtcct aattcccaaa gtctaacata caaatatgtt aggttgcatg gcagtgggaa 57601 attagatttc aagtgaaatt aaggttgcaa taaaatgatg gagagattat cttaaatggg 57661 tgggatcaat gaaatcacaa gcttccttat aagtgaaaga agaaggcaga agaaaggcaa 57721 ccatggaggt ggtggcatga gaaattactc aacatcactg acttttaaga tacaagaatg 57781 aggacccagc gcggtggctc acgcctaatc ccagcacttt gggaggccgg cgtgcgtgga 57841 tcacgaggtc aggagatcga gaccatgctg gctaacatgg tgaaacccca tccctactaa 57901 aagtccaaaa aattaactgg gcatggtggc acgtgcctgt agtccaagct actcaggaag 57961 ctgaggcagg agaatcgctt gaacccagga ggcagaggtt gcagtgagct gagatcgtgc 58021 cactgcactc cagcctgggc gacagaaggt gactccatct caaaaaaaaa aaaaagatat 58081 aagaatgagg tcatgttcca aggaataaag gtggcttctg catgctgaaa aaaatcaagt 58141 acatagattc tgccacagag ccctcagaaa gactgcagcc ctgcccaaaa cttgatgtta 58201 gccctgtgag tctcatttaa gccttctgag ctccagtact gtaagattac cagtcacttt 58261 actgtaagat atgaagtttg tggtaattgc ttacaacagc aagaggaagt ttatatagta 58321 attgtatcac gaaaatgaga accataattt acaactgctt ttaatactgc acttggatgt 58381 ttgaaatcac gtacatggaa atgatcagta tgtgtatgag ggaagatagc aaattgatgc 58441 caaaataacg caaatgcaaa tcttacactc atttctatgt aggtttcatt taatctttga 58501 aattaaaatg aaattaaagg attatgatat tttgatgaaa ttagactaaa atgaacaata 58561 acaaaataag aacttacata tattccttat atggtcaata atgaagtgat agtggaaaaa 58621 aacaaggtca aatgaaggtg atgatttagg aagttggaaa gatagcttaa aatacaaaat 58681 ggtgtataac tagtgaacac ttagacacac tgattgatga acttcagctt ttggcttgat 58741 gagagcataa aatgagagca gctgaggttt gcaaatttgt aatctgcttg tggaaaaaca 58801 ggggaaaaca catctcagcc taataagatt tatctactaa agagtcaaga attgatccat 58861 ttgtccttgt aattcaaaag ctaattcaaa tactgatttg atgtattgtg tgaacaatca 58921 ttgctgatta tcatcgcata cctggcattc tcttttatct gatatctaaa atatttggta 58981 attcctggac tttctctttt caaacccagt atggattaat ttcaatctta gaacagttgt 59041 ctttgagaaa ttcttccctc tactgcatct gtgaatgggc atagcatggt tacctacata 59101 ctgtcgcccc agagaacatt tgttgaatta aagccaaagt ttaaagcaac agctttaact 59161 cactggtttt actaatgttt tcctccccat tagccacaac aatattgata ccctcacacc 59221 ctttaacata aagcttggtg ttgtctattt ttcacgtgct gtcatctata tgatctcagt 59281 attttaaaaa tcagcttcca gcccatatgg tggctcatgc ttgtaatacc agcagttgaa 59341 gaggctgaaa tgagaggatt ctttgagccc aggagttcaa gagcaacctg ggcaacataa 59401 caagacccag tcttcatcaa aagttaaaaa aaaaaaaggt ggccatggtg aggtgcacct 59461 gttgtcgtag ctatttggga ggccaaggtg gaaggattgc ttgagcttgg gaggttgagg 59521 ctgcagtgag cagtgattgc accactgcac tgcagcctgg gcaacaaagc aagaccctat 59581 ctcaaaaaat atatataata aaaataaaaa tcagctctca ttgatttcta cataaatgtg 59641 aacaggtgat gtccatatag acataaataa taatatatct gacaatggtc catatgatct 59701 tcaaaatgta aaatgcctat ctgtgtaatt gactggttag tctcattaat gaatatagat 59761 tcaattctac tttcttgttc tagataaatt atataatcta gcttttcctt tcactcattt 59821 actgataaca acaggaagaa tgacaagata tctattttgg aaaattactc tggtaggagt 59881 aaagatgaaa caatgataga attgcatgga aaactagaaa aaagtatggt cttctgatat 59941 tatatcacat catataataa agccctcata caactcagat attttatcta aaaatgttat 60001 tttcatctta ggaatgatca cagcatgaga ctagaattgt attacaatga ctctcacaag 60061 cacatgtgct aaaaaggaga ggaaaacatc attactgata ttttaaacat atgttttact 60121 ttccatcaac gtgaacctca acttgatatg atgcagattg aaggaaatca cccataattc 60181 catatgaaga aggcctgtga tattttatgg gaaaataaat agagaaaatg ctaacagaaa 60241 ccctattaag cattaagctt tatggagcaa agacaaatcc agtggtgaaa gatacacact 60301 cgagttctgt ttgttgtctt ggaacaatac ggtttagagg tgactggtgg gtgaggagaa 60361 catatgcgag ttcaccaaac agaaaagctg aatgaggcaa tgcctctttc tgaccatatc 60421 tcttactcag ataactatat aatttattgt ccagtaaagg gtatatttaa aaatcatatt 60481 aaaagtcatg caatgaagtt gtccagggaa atcaagactt aagagtctca ctctgacaat 60541 aatgaatggg gggggttccc tcaagaaaga ctaggacatg actccacact ggcaggtagt 60601 agtaccagaa aagaacccat ggaaaatctt taccttatgc ttgaggtagg gaccaggcta 60661 aagtgaaagc cagacataaa attcaatcta aaatatatcc aaaattgaag aaaatatgtg 60721 ttgtacaggc atagaatgtc tttcctggat cattgaaata gtaagataaa ttcaattttt 60781 tacattgttt tattttcctc cagttagggc ttgaggtttg tctctggaga gagactgtca 60841 attggagccc tgcctttctg gggttctggg cagggggttg tggatgctta acatgtgcct 60901 ttcacaggac acttccttac cccagcagtg gccaggtgtg catcccacga gcaggcctcc 60961 ctctcacaga aaatctgttg agactaggag atgcctggtg gctgttgcgt gacctgtgtc 61021 ctgtgtattt ctgacaagag ccactctcag agaccctggc caggaggaga gttaggttcc 61081 agtgtaggtc agctcagaca catggaggcc acaggaccaa acatgggaaa tcacagaagt 61141 agttttatta ctcacagatc cagagagaag agggtagctg agaagagggt ttagctgtgt 61201 ccccagccaa atctcatctt gaattcccac atgttgtggg agggaacagg tgggaggaaa 61261 ttgaatcatg gggacaggtc tttcccatgc tgttcttctg atagtgaata agtctcacaa 61321 gatctgatgg ttttataaag gggagtttcc ctgcacaagc tctcttgtct tgtctgctgc 61381 cacgtgagac ctgcctttca ccttccacca tgattgtgag gcctacccag ccatgtggaa 61441 ctgtgcacct attaaacctc tttcttctgg aaatcaccca gtcttgggca tgtatttacc 61501 ggcagtgtga aaatggacta atacagtagc acacctcata gggctgaaca aaatgaggaa 61561 gataagtggg gagcaagaga gaaaaaagtg gtctgtggga ctccagcctt tattgagccc 61621 agaacattac ccaaataagt tttccacggg gctctggtca gtggggtgag agccagtagg 61681 cacatttctt ggctgcagct gcaactgagc aggtcactct ggcgtgtggg ggctgtccat 61741 gtgggctgtg aggtctgtgg ggtgagtcag gtaggttgta tccaacagtt ccacaacggc 61801 tagtcaccag gaggaggcag ctgtgtaggg tcaatatctg ggccagccac actgaggaac 61861 tgtgagggtt agaactggaa atcatcaagg gaatctgaac ccagctacca tatgagagag 61921 ttcaacttac gttcaatgtg aatgccatgg caatattaaa aggtaagaat tcgctccata 61981 cgtgtttgag gtaaatagga gaaacctaga atttatgtaa acagtgagaa gattggatgc 62041 gttttccgtc acatatttta atactagcag catattatat atgtcaatcc atcaggcatt 62101 cagaagtact tgcttatgaa aactttttgc accatcagac aaaagacaag ggtagaagac 62161 atttttaacc ctacaaacac tagtaaatta aaaacagaag gacctttatg tcctaatatg 62221 tctatgttgt gaaaggctgc cctgtgaaat acaggatttc ttaaacatat tttaaaaatc 62281 atagctgtca atatttttta gaaatccatt taaattttct cttgcttttt tacaattcct 62341 atttatttat ttagtggttc tgttgatttt gatgtatagc ctaaacttta tatttcttta 62401 aagtatgttt tatacaactt tatgtaaaat gtttgagtat cttcacgttc tcaccctgtc 62461 cttttgtttt gctcttatat ggtggccttg agtcttttct ctggcttttc aaacctagta 62521 agactaagac accaaagtaa ctttgcccgt ggtttcgtaa tgccttctaa agcacatcct 62581 aagctctcgt gcatacaggg gtctcctttg agctctatgc ttttgagatc ccatatacct 62641 aaattccagt actccaaatc agtactgctc agttttagtt actaagttta aaaatgtatt 62701 ttaataacaa gttagtttag ttcactcttg cttctttctt tactgctggt atacatgtat 62761 attcctttaa ataaatcttg gaatttattt aaaaatttta aattatacta atgaaactgt 62821 atattgttgt ggattcatag gtgaatttgg aaagaatttg tctttgtgat actaaatcct 62881 ttttatccaa gaatcatatg tgcctttata tttattccag tctatattta tatcactgag 62941 taaatatata gaaatgtaga tacatacagc tgtagctata gatagataca aatatagata 63001 taacatgtta aatctatatc tatcccatat aacatatatg catgttatat gtgtgtgtat 63061 atatatatat gtttgtgtta ttaaagagct cccttaaaat ttttctttta tttcctatat 63121 aattttaggt tgagcttgaa ttttctttgt acaaacaagc aaatatttat actagtttta 63181 atactgaggt ttagacattc tatcttatat tagcattgaa tattttcaca attataaata 63241 ttatctaata ttaataatgt aacttaaaaa tatttaaaat tttacctttg aattatttta 63301 ttgttgaatt taaattcctt taagtatgac agtaaatttc tattttatgc tttctctatg 63361 catatgaaat taatctattc acttctctac ctttatgtag taacatatga aaatcaggcc 63421 tctgttcttc taatggacat acacatgttt gcatatagaa tatcagactc tttatagtat 63481 ttaaaatctt taaagacgtg aatatgacct tttaacaaat atattttagc gtgtactgag 63541 aatcccctat ttatttttta tttgggctaa tcaatatgat tattaatatt attggattac 63601 caaatttgga atcacacttt catccccaag gtggatattt gttttatttt tttgccaatt 63661 tcttgtctta ctgtttcaaa tactgttgga tattattttt attttatttg gcattttagt 63721 atcaatattt gtaagtgatg tactctacat attttttctt caatatctgg tgggttttat 63781 aattactgct atattggatt tgtagtagac attgagaaaa attattcctg catgttttat 63841 agctgtatga aggaaactaa tatattttac cccaaaatat atttccttga tatatttcaa 63901 aatggctatt gagaagggct ggaaatgcaa acatagctgc aaagctgtct tggggagatt 63961 tgcatcagta gagaatctgc cttgatgcag ccaggctttc tctgagatct gttcccttgt 64021 ctggatctag gaaagattaa ctgagggtct gaggtctgca aaggtctgaa agaaacattt 64081 tctgtctatt atctctgagg actgctccca gtgaggtttc acctacgtaa taagtccact 64141 gttgctagcc agggtccttt tctcacataa cttttttttt tttcctctgt gatccaagac 64201 cccattcttt ctgtaaactt catgtggtag ttaaacttct gcacccatcg tgtgtctggg 64261 tcttcattct aagggctcca gtgtacacac attgcagaaa cctgtatgcc ttttctacta 64321 tttatctgcc tcctgttagt gattttcagg gaaacttcag aaggcaaaag ggacattctc 64381 ctttagccca tactcagaca aaatccccca acatttaact gattcctaat agcttaaaat 64441 cactttgaaa actccacata tttataactt ttcttccctc tatgatttct gttcagcttg 64501 ggttttgttt tttattccat ttacttcatc ctcgaaagac ctattttatg tctatttatt 64561 ctcatttatt gacattgaga aaagaaaata actttcatgt gagaaacgca agtcctttta 64621 aataatcagg cccagagaga tattcagatg agacagcagt tctgttctgc tcctctttga 64681 gctgtgtgtt catctaggct gccgctgttg ccacagtagc tataaattaa ccaataacgc 64741 cacaccagac actataatcc acacccaata atagtgtaac agtgtatagc cagtcactaa 64801 taaatgttat ttccataagc caatgagaat ttgtgacaaa cctctttgca tcatcccact 64861 tcttgtccct tttttgcctt taagaaactg cttgttgcaa agctccaaag ggagttcata 64921 tccaaggata cttgggtctg ttccttccag gcagctgtcc tcattgtggc tcaagtaaac 64981 tctttgaatt acgttttgtg cttcagcccc ttccacttag attaacaaca tggatttgtg 65041 tcaccatgta cagcaattaa aatgtttaca cttttcccct cgagggcact gatgtgtttt 65101 cctgagcact tggaatagct acttagtgtt tactttctag aatatggttt ctcaaccttg 65161 gtgctactta cctttaggac cagaggattc tttgttgtgg gaggctgccc tagcaatgct 65221 aggtgtttcg tttgacctct aaatttcaca cctccaccag tcttgacatc cccacaataa 65281 ccctagacat tgacaaatgt ctcctgggga aaactccacc agttgacagc caaagttctt 65341 gaaatattgg aatcgtcaat tgagttttta tgttatccaa aacaaatatt tttctttgtt 65401 tttaaacatc tacttccatc tacttatcta cttattttta cttttattta taacttaatt 65461 ccatcaagga gagagagtgc attttgtgtt atgctaaatt tttgaagaat gtattgattt 65521 tttatggcct gatatatgga tgatatgtag atattacatg tttgtattat caaatttcag 65581 ggtgataata aaataaatac ttataatatt tatattgtca ctgtatatta gttatttctt 65641 tcttcactac aggagttttt caacctatag gctatttttc aattctaggt tatccagtag 65701 attttgaaat gttatgatta aatatctact tctcaagcat tcatctttgc aaaggaatca 65761 atcccaagct cttataatgc acatcatata aagggcagat tagtcaatat atggttcaga 65821 aataattatg taatatttat aagaaaatta aaaatttaga tccttaactc agataacaat 65881 aatccaaatt aaaatttgat ttaattacat aatttaaaat gacaccagaa tactagtaaa 65941 aatgtagata agtttatata atccttttta gctgtagaac tttattagca taaattcaaa 66001 tacaggaacc aaagtaagat tgagacctat agtcaaaggt taaaatgtac acattatagg 66061 ggcatgatta aactaattta aagcatagta acatggagaa atattgcaaa acatacattt 66121 tactgaatta attgttaata tctaatcatt acatgagaac aaaggtaaag agtagctaca 66181 cacacacaca cacacacaca caagtgcaat attttcagta aacgtgatgt tcagctacac 66241 tacaaatcac acctatgttt tctccacaga aaagtaaaga ttaaaaatca caataatatt 66301 tattgtacat atggaggtaa agatactcaa aatattaccc taaaatactt ttttttttga 66361 gatggagtct tgcttttatt gcccaggctg gagtgcaatg gcacaatctt ggctcactgc 66421 aacctcagcc tcccagggtc aagttattct cctagctcag cctcccaagt agctgagatt 66481 acaagcatgc accaccacac tcggctaatt ttttatattt agtagagacg gggtttcacc 66541 atgttggtca ggctggtctc gaactcctga cttcaggtga tctacccact tcagcctccc 66601 aaagtgctgg gattacaggc atgcgcccgg ccaacttttt gacatatttc aagatggcta 66661 ctcggaagac tggaaatagc ttcttctaca agaatagctg aaaagctgtg tttgttgggg 66721 agatttgcat ttgtagagaa aatctgcatt gatatagaca ggctttccct gagatactcc 66781 cttgtctggg tttaggaaag attaactgag tctggcacgt ttacatttct aaaaaccatt 66841 tcctatcttt acttcccaag aggagggctg ctccctgtga ggtttcatcc atgtaacaag 66901 accacctctg ctgccaggct cctctttctt ccttgtcgtc acctgccttc tgcaaagcct 66961 gatttagcaa agtacagctc tgtgttttct gtaacctcaa gacagcatag gcgtgttgac 67021 taccttgcct ttcctggagt ttttatacat atacagtata tatttgtata tcaatttata 67081 atatacaaat atttgtatat acatatttat gtatattatg taaactccaa gtgcatactt 67141 gtgcacgtaa ttatatctgt aaaccttttt tcctgttaat ttgtacatta tcagtttgtt 67201 tgatagactc aaataattaa agcttcaagg gaaaaattta aactttccta tagagaaaag 67261 acatatatgt gacaaataat atttagagtg taagacgctt tttaaaggta tatttgcaat 67321 ttgtgtcaaa acatttaaat atacatttgt tactttataa aatttcaaat aatttaagct 67381 aaatacatag tatatgcaga aaatttagca atatttgtat gtagcacctt actgtgcatt 67441 actgtaacca gctgtctaat ataaagaact aattaaggta gtacctactt ttcaaatatc 67501 gcattttttc acagacctat taaataagac aaataacatt taaactttat ttttaaattt 67561 gcagaatagt atttttcagc agatggttta ttttagcaaa ttccatcttc acattgtgct 67621 atgcttttat gagttccagc tgttaacgga taatatttta ctgctgaatc tatcatgtgt 67681 gatataattg ctcattatgt gccttaaaac acaagcgata tggttatttt caacttggag 67741 caaattaaaa tcttatcagc aatttaaaaa gtctagagtc gtcttcttct ggttaatttt 67801 tttaaacttg tatttttctc tttatgtttt tagtgagttg tcttatcaag gagaagaact 67861 caagctgatt attctttttt tttctcttcc atccacctcg ctggtgtgtg aataatttca 67921 tttctcagaa aatgttcttt catatccatc ttacaagatg agagaccttt taacatcttc 67981 cattcggatg tgataccagt aatggaaaat attccagctt catgaatatg gtgatacaaa 68041 tagttatccg tctaacctct gtcagtgcca aatgtttact ttactcagtg aattactcag 68101 ctgactggta atttcttctg aaatcactaa tgagaggatc agaggtctgg ctgttgtctg 68161 tacctcgtat gactcccagt gcagacaatt gtttctatgg agcacagaca gttgaatgga 68221 ttgacttcct gcctagaata gtttctgctg tgcttcttat ccttcttatg gagatttcag 68281 attatctgaa ttgcttttct atcttaagaa aaaactcaac aattctccca cctgagagga 68341 aagtaaactt tagtaagtta gcagaagcaa tccgtaaagt ttttacattg tttgttgtaa 68401 aatgcagcgt tggtgtctcc atcactaacc ttttctatcc ctcattgctg tttctttgac 68461 tgcaatagga tacctctagg caaatctgta ttcccgagac agagtgccct ttccgttagc 68521 tataagtaca ctcaatggta ggctgaaatg atagttttta tctatggtga aatggaatca 68581 tatcagtgat ttttttaaag gaattttaac tcttgctatg gtttgaatgc ttgccccttc 68641 caaatctcct gttaaaattt gatccccaat gttgcaggtg gggcttactg ggaggtgttt 68701 ggtcatgggg atggaacttc atgaatggat aataccctcc cttaggaatc tcaagctatc 68761 ctccctcctc ggtgccctca ggaatgaatg taccattctt tattcaacta taattccccc 68821 acccatccct tttgagatat taattaaatg tatgttacac tgctgcatat tgtctcacgt 68881 atcagtgagt ttctggcttt cttattttag tttacccttt gtcctttagt ttgtaaagct 68941 tctaattttt ctatatattt tctgatgtta gggtaaaata catgacttat tctatctcat 69001 ggaattttta tttaaaatat ttatttttca tctatacgtg tcacattttt cattttataa 69061 cttccatttt tctcctatgt tcaattttca tttaagtact ttgacatata tatgtattta 69121 tctatatgta tttataaaat atatttactt taaggacctt gaaaattcct tcttctgtca 69181 tttataaatg gcttattttt atcctgttaa tatatatctt aataatatat atcttctggc 69241 ttctttgcat gtcagagttt tttttggggg ggtattttga tgttatgcta ttgaatatct 69301 agattttatt ggctaccttt gaacaatgtt gtggcaggca gttcagtaac ttcaggatga 69361 gtatttttct gttgttgttt taaatcttct ctttaaactt tgttgagtta gtctagagcc 69421 atctgtaatt tggagctaaa tgagcactgt cactagggca taacctccag tggtctttac 69481 tgaatatcct ggaggtacag aggggattcc cttctctggc tggtcagagc taacatgtct 69541 tcctgtcatg tgacgccagg gaagtgttct tccaactccc tggtagagtc ctttgctgag 69601 ctccttagaa tttcatccta tgtacatttg gcttagggac ttgggagaaa ccttaggctg 69661 attattggtt cctttttctg taaacgttct cttctactac acattccagc tgcttaacat 69721 tttggttttt atctggttcc tcagtgcaat gacaatgtct gctctctctg ggattcctct 69781 ctactgctgt cacggagaac ctgggaataa agcaggactc attctggctc cttcttttct 69841 cttgcggagc acagtcctgt gctgcctgat gttcagtatt tcaaaaaaag tttcatatat 69901 tttgtccagt ttactattct ttaactctaa aagagtaact ccagtcccag ttacagcatc 69961 atgttctgta actctactcc ttgttgcttc attctgccat tgtctggtat gattgcccct 70021 ttcccttctg taatcaggcc aagagcataa cataatacta gttataactg cacagcttgc 70081 ctccgttgtg taaaaaaatc actgagactt aactgtgtcc aactttttaa atgtgaatat 70141 aagtacaact aaagctatat tttgtttaat atttgcattg catgcttttc cattatttag 70201 tttcaaaata tgtgaaatat aaatataaat tataaaaact ttaagagagt acatttaaaa 70261 aatctggtct gattatgttt taactggttt attacaacat gcattcttga attcagggtc 70321 taatataatt ggtacatttg tctatttgca aaaaaaactt gacaatattt taaaattaat 70381 ttatccaact cacaacttat atgcttctgc tgttgtatgg aagatgcatt ttaaacttta 70441 tgagctagca ttctgttata cagtcgatgt ccaattaaat ttctctctat gtttatttct 70501 ttcattaaaa aaagcgttct tctaactgca aactttcatc agggatcata gctcttctac 70561 ctgaagaata atctttagta tttcttatcc tgtgggtctg cttgggataa attctttatt 70621 gtatctttgc ttttgatgga tatgtccacc aagtagacag ttctaggtcg gcacttattt 70681 tatttcagga cttgaaaggt atcaatacct cacttgttgg ctttcattgt tcatttgaga 70741 aggttgttat cagtcaactc tttctcttta tagttagccc aattttttta tcaagtgctt 70801 ttgacatttt tcttttactt ttcagaaatt gtcccatcat gtttctaggt gtgtcctctc 70861 tgtgtgtttt catttggttt gcaaagcctc ctgaacctgt ggattaatat tattggtcaa 70921 ttttgataaa acctctaaca ttgccactta aaatgctgtt cagaccagct gttttgtcct 70981 tcttagattt caacgtgtta gattattact gtatgcttta tattttttaa ataacctttc 71041 tctacttttt ttttagttgg ttaatctgta ttagtgtatc ttttgctttt ttattttatt 71101 ttattttatt attatacttt aagttttagg atacatgtgc acaatgtgca ggattgcaac 71161 ataagtattc atgtgccata ttggtgtgct gcacccatta actcgtcatt tagcattagg 71221 aatatctcct aatgctatcc ctcccccctc cccccaccac caacagtccc cgaagtgtga 71281 tgttcccctt ccggtgtccg tgtgttctca ttgttcaatt cccacctatg aatgagaaca 71341 tgctgtgttt gcttttttgt ccttgcaata gtttactgag aatgatgatt tccagtttca 71401 tccatgtccc tacaaagcac atgaactcat ccttttttat ggctgcatag tattccatgg 71461 tgtatatgtg ccacattttc ttaatccagt ctatcgttgt tggacatttg ggttggctcc 71521 aagtctttgc tattgcgaat aatgccacaa taaacatacg tgtgcatgtg tctttatagc 71581 agcatgattt atagtccttt gggtatatac ccagtaatgg gatggctggg tcaaatggta 71641 tttctagttc tagatcccta ggaatcgcca cactgacttc cacaatggtt gaactagttt 71701 acagtcccac caacagtgta aaagtgttcc tatttctcca catcctctcc agcacctgtt 71761 gtttcctgac tttttaatga ttgccattct aactggtgtg agatggtatc tcattgtggt 71821 tttgatttgc atttctctga tggccagtga tgatgaacat tttttcatat tttttggctg 71881 cataaatgtc ttctttcgag aagtgtctgt tcgtgtcctt cacccacttt ttgatgggat 71941 tgtttgtttt tttcttgtaa atttgagttc attgtagttt ctgaatatcg gccctttgtc 72001 agaagagaag gttgcgaaaa ttttctccca ttttgtaggt tgcctgttca ctctggtggt 72061 agtttctttt gctgtgcaga agctcttttg tttaattaga tcccatttgt caattttggc 72121 ttttgttgcc attgcttttg gtgttttaga cctgaagtcc tttcccatgc ctatgtcctg 72181 aatggtattg cctaggtttt cttctagggt ttttatagtt ttaggtctaa catgtaagtc 72241 tttaatccat cttgaattaa tttttgtata aggtgtaagg aagggatcca gtttcagctt 72301 tctacataag gctagccagt tttcctgaca ccatttatta aatagggaat ctttccccat 72361 tgcttgtttt tgtcaggttt gtaaaagatc agatagttgt agttatgtgg cattatttct 72421 gagggctctg ttctgttcca ttgatctatg tctctgtttg gtaccagtac catgttgttt 72481 tggttactgt agtcttgtac tatagtttga agtcaggtag cgtgatgcct ccagctttgt 72541 tcttttggct taggattgac ttggcgatgc aggctctttt ttggttccat atgaacttta 72601 aagtagcttt ttccaattct gtgaacaaag tcattggtag cttgatgggg atggcactga 72661 atctataaat taccttgggc agtatggcca ttttcatgat attgattctt ccaacccatg 72721 agcatggaat gttcttctat ttgtttgtat cctcttttat ttcattgagc agtgttttgt 72781 agttctccat gaagaggtcc ttcacgtccc ttgtaaggtg gattcctagg tattttattc 72841 tctttgaagc aattgtgaat gggagttctc tcatgatttg gcactctgtt tgtctattat 72901 tgttgttcaa gaatgcttgt gatttttgta aattgatttt gtatcctgag acttttctga 72961 atttgcttat cagcttaagg agattttggg ctgagaaaat gggtttttct agatatacaa 73021 tcatgtcatc tgcaaacagg gacaatttga cttcctcttt tcataattga atagcctttg 73081 tttccttctc ctgcctgatt gccctggcca gaacttccaa cagtatgtgg aataggagtg 73141 gtgagagagg gcaaccctgt cttgtgccag ttttcaaagt gaatgcttcc agtttttgcc 73201 cattcagttt tctattgact gtgggtttgt tttagatagc tcttattatt ttgagatacg 73261 tcccatcaat acctaattta ttgagagttt ttagcatgaa gaattgttga attttgtcaa 73321 aggccttttc tgcatctatt gagataatca tctcgttttt gtctttggtt aggttgatat 73381 gctagattac atttattgat ttgcatatgt tgaaccagcc ttgcatgaca gggatgaagc 73441 ccacttgatc atggtggata agctttttga tgtgctgctg gatttggttt gccagtattt 73501 tattgaggat ttttgcatca atgttcatca aggatattgg tctaaaattc tctttttttg 73561 gttgtgtctc tgccaggctt tggtatcagg atgatgctgg cctcataaaa tgagttaggg 73621 aggattccct ctttttctat tgattggaat agtttcagaa ggaatggtac cagttcctcc 73681 ttgtacctct ggtagaattc ggctgtgaat ccatctggtc ctggactctt tttggttggt 73741 aagctattga ttattgccac aatttcagag cctgttattg gtctattcca agattcaact 73801 tcttcctggt ttagtcttgg gagagtgtac gtcttgagga atttatccat ttcttctaga 73861 ttttctagtt tatttgtgta gaggtgtttg taatattctc tgatggctga ttgtatttct 73921 gtgggattgg tggtgataac ccctttatca ttttttattg catgtatttg attcttctct 73981 cttatcttct ttattagtct tgctagtggt ctatcaattt tgttgatctt ttcaaaaaat 74041 cagctcctgg attcattaat tttttgaagg gttttttgtg tctctatttc cttcagttct 74101 gctctgattt tagttatttc ttgccttctg ctagcttttg aatgtgtttg ctcttgcttt 74161 tctagttctt ttaattgtga tgttagggtg tcaattttag atctttcctg ctttctcttg 74221 tggtcattta gtgctataaa tttccctcta cacactgctt tgagtgtgtc ccagagattc 74281 aggtatgttg tgtctttttt ttcattggtt tcaaagaaca tctttatttc tgccttcatt 74341 tcattatgta cccagtagtt attccagaac aggttgttca gtttccatgt agttgagcag 74401 tcttgagtga gtttcttaat cctgagttct agtttgattg cactgtggtc tgagagacag 74461 tttgttatga tttcttttct tttacatttg ctgaggagag ctttacttcc aagtatgtgg 74521 tcaattttgg aataggtgtg gtgtggtgct gagaagaatg tatattctgt tgatttgggg 74581 tggagagttc tgtagatgtc tattagatct gcttggtgca gagctgagtt caattcctgt 74641 gtacccttgt taactttctg tttcattgat ctgtctaatg ttgacagtgg gttgtgaaaa 74701 tctctcatta ttattgtgtg ggagtctaag tctctttgta ggtcactcag gacttgcttt 74761 atgaatctgg gtgctcctgt attgggtgca tatatattta ggatagttag ctcttctcat 74821 tgaattgatc cctttaccat tatgtagtgg ccttctttgt ctgttttgat ctttgttggt 74881 ttaaggtgtg ttttatcaga gactaggatt gcaacccctg cctttttttg ttttccattt 74941 gcttggtaga tcttcctcca tccttttatt ttgagcatat gtgtgtctct acacgtgaga 75001 tgggttcctg aacacagcac attgatgggt cttgactctt tatccaattt gccagtctgt 75061 gtcttttaat tggagcattt agtccattta catttaaagt taatattgtt atgtgtgaat 75121 ttgatcctgt cattatgatg ctagctggtt attttgctcg ttagttgatg cagtttcttc 75181 cttgtctcaa tgatctttac attttggcat gattttgcag tggctggtac tggttgttcc 75241 tttccatgtt tagcgcttcc ttcaggagct cttttaggtc aggcctggtg gtgacaaaat 75301 ctctcagcat ttgcttgtct gtaaagtatt ttatttctcc ttcacttatg aagcttagtt 75361 tggctggata tgaaattctg ggttgaaaat tcttttcttt aagaatgttg aatatcggcc 75421 ccctctctct tctggcttct agagtttctg ccaagagatc cgctgttagt ctgatgggct 75481 tccctttgtg ggtaacccga cctttctctc tggctgccct taacattttt tccttccttt 75541 cacctatggt gaatctgaca attatgtgtc ttggagttgc tcttctcgag gagtatcttt 75601 gtggcattct ctgtatttcc tgaatctgaa tgttggcctg ccttgctaga ttggggaagt 75661 tctcctggat aatatcctgc agagtgtttt ccaacttggt tccattctcc ccgtcagttt 75721 caggtacacc tatcagacgt acatttggtc ttttcacgta gtcccatatt tcttggaggt 75781 ttgttcgttt ctttttattc ttttttatct aaacttccct tcttgcttca tttcattcat 75841 ttcttcttcc atcacttata ccctttcttc cagttgatca catcggctcc tgaagcttct 75901 gcattcttta cgtagatctc aagccttggc tttcagctcc atcagctcct ttaagcactt 75961 ctctgcattg gttattctag atatacattc gtctaaattt ttttcaaagt ttttaacttc 76021 tttgcccttg gtttgaattt cctcctgtag ctcagagtag tttgatcgtc tgaagccttc 76081 ttctctcaac tcatcaaagt cattctccac ccagcttttt tccattgctg gtgaggaact 76141 gcgttccttt ggaggaggag aggtgctctg ctttttagaa tttccaattt ttctgctgtg 76201 ttttttcccc atctttgtgg ttgtatctac ttttggtctt tgatgatggt gatgtacaga 76261 tgggtttttg gtgtttatgt cctttctgtt tgtaagtttt ccttctaaca gacaggaccc 76321 tcagctgcag gtcttttgga gttttctaga ggtccactcc agaccctgtt tacctgggta 76381 ttagcagcgg tggctgcaga acagcagatt ttcatgaacc gcgaatgctg ctgtctgatc 76441 gttcctctgg aagttttgtc tcagaggaga acccggccat gtgaggtgtc agtctgcccg 76501 tactgggggg tgcctcccag ttaggctgct tgggggtcag gggtcaggga cccacttgag 76561 aaggcagtct gcctgttctc agatctccag ctgtgtgctg ggagaaccac tgctctcttc 76621 aaagctgtca gacagggaca tttaaatctg cagaggttac tgctgtcttt ttgtttgtct 76681 ctgccctgcc cccagaggtg gagcctaaag aggcaggcag gcctccttga gctgtggtgg 76741 gctccaccca gttcgagttc ctggctgctt tgtttaccta cgcaagcctg ggaaatggcg 76801 agcgaccctc cccaagcctt gctgccgcct tgcagtttga tctcagactg ctgtgatagc 76861 aatcagcgag actccgtggg cgtgtcaccc tctgagccag gtgcaggata taatctcctg 76921 gtgcgccgtt tgttaagacc atcggaaaag cacagtatta gggtgggagt tacccgattt 76981 tccaggtgcc gtctgtcacc cctttctttg actaggaaag ggaactccct gaccccttgc 77041 acttgccgag tgaggcagtg cctcaccctg cttcggctca tgaactgtgc actgcaccca 77101 ctgtcctgca tctgctctct ggcactccct agtgagatga acctggtacc tgagatggaa 77161 atgcagaaat cacccatctt ctgcattgct gacactggga gctgtagacc ggagctgttc 77221 ctattcggcc atcttggcta cacttggtag tttcttttcc ctctgcttct gggttctgag 77281 agtttgtcac taacatagga ttccagaaca ctgctgcagg gttctgagtg attgttgctc 77341 acatgggatt caaaaacact cctgctgggt tcagagtgtt atccctcaca tacgattcca 77401 gaacactgct atgaggttct gaatgtttgt ccttcacaaa ggattccaga acactgctgc 77461 tgggttctga gtgtttgtcc ctcatatagg attccagaac actgctgctg ggttctgagt 77521 gtttgtccct cacataagat tccagaactc tgctatgaag ttctgaatgt ttgtggctca 77581 cataggattc cagaacactg ctgctgggtt ctgagtgttt gtccctcaca taggattccg 77641 gaacaatgct gctgggttct gagtgcttgt cccttatatt ggattccaga acaatgttat 77701 gagggtctga atgtttttcc ctcatgtagg attcaagaac actgctaaga gggtctcaat 77761 gtttttccct cacaaaggat tgcagaactc tgctgctggg ttctgagtgt ttgtccctga 77821 tataggattc cagaacactg ctatgagggt ctgaatgttt ttccctcaca aaggattcca 77881 gaacgctgct gggttctgtt tgtttgtccc ccacaaagga ttccagagca ctgctgctgg 77941 tttcttagtg tttgttccac acatgattcc agaacacttc tgcgatggtt tgaatatttc 78001 tccctcagat aggattccag tacacagtgg ctgggttctg agtgttggtc cctcacatag 78061 gattccagaa cactgcttct gggttctgag tgtttgtcac tcacatagga ttccagaaca 78121 ctgcttcgag ggtctgagtg tttgtccctc acaaaggatg ctggaacact gctgctggtt 78181 tctgagtgtt tgtcactcac agaggattcc agaacactgc tgcttccaga acactgctgc 78241 tgggttctga gtgtttgtcc ctcacatagg attccagaaa actgctatga gtgtctgaag 78301 gtttgtccat aacaaaggat tccagaacaa tgctgctgga tctgaatgtt tgtccctcac 78361 acaggattcc aggacactgc ttcgagggtc tgagtgtttg tccctcacac aggattccag 78421 accactgctt ctgggttctg agtgtttgtt ccacatatag gattccagaa cacagctaca 78481 aggctatgaa agtttgtctc tcacaaagga tttcagaaaa atgctgctgg gttctgagtg 78541 tttgttcctc acataggttt ccagaaaact gctgctggga tctgagggat tgtccctgtc 78601 attgagtacg agaacactgc tgctgggttc tgaaggtttg tccttcactt agaattgcag 78661 aatactgctg ctaggttatg agggtttgtc cctcatgtag aattctagaa ctctgctgct 78721 gggttctgag catttctcta tcacatgaga ttctggaaca ctgctaaaat gtaggaatgt 78781 ttgtccctca caaagagtcc agagcaccgc ttgtgggttc tgagtgtttg tccctcacat 78841 aggattgcag aacacagctg ctaggttctg agtgtttctc ccaaacatag gattccaaaa 78901 caccgctcag agggtctgaa agtttcttcc tcaccaagga ttccagaaca ctgctgctgg 78961 gttctgaaag tttgtccctc acatacgatt ccagaacact gctatgaggc tctgaatgtt 79021 tgtccctcaa agggattcca gaacactgct tttgagttct gagtgtttgt ccgacacaaa 79081 ggattccaga acactgctgc tggcttctga gtgtttgtcc ctcacatagg atttcagaac 79141 actgctatga gggtctgcat gtttttccct cagaaagcat tctgtatcac tgctacgagt 79201 gtctgaatgc ttgtccctca cataggattc cagaacactg ctactgggtt ctgactgttg 79261 gtccttcaca taggattcca gaacactgct ccgagggtct gaatgtttgt ccctcacata 79321 ggattccaga acatttgctg ctggtttgtg agtgtttgtc cctcatatgg gattccagaa 79381 cacttctgct gggttctgtt tgtccctcat ataggatacc agaacactgc tattggcttc 79441 agagtgtttg tccctcacat aggattccag aaaacttcta agaggttccg aatgttttcc 79501 ttcagatagg attccagaac actgctgctg ggttctgaga gtttgtccct cacataggat 79561 tccagaacac tgctaagagg gtctgaatgt ttgttcctca gataggattc caggacactg 79621 ctgctgggtt gtgtgtgttt atcactcaca tagaattcca gaacactgct acaagtgtct 79681 caatgtttgt ccctcacata gaattccaga atattcctgc tgtggtctga atgtttgtcc 79741 ctcacatatg attccaggac gctgctgctg tgttctgcgt gtttgtcccc cacataggat 79801 tcaagaacac tcctgctgtc ttctgaacgt gtgtccttca cagaggattc cagaacactg 79861 ctactagcct ctgaattgtt gtcccccaca gaggattcca gaacactggt actagggtct 79921 gaatgtgagt ctctcacata ggattccaga acactaatgc cggggtctga atgtttgtcc 79981 ctcacctagg attgcagaac actgctacga ggttctgaat ctttgtccat cacgtagcat 80041 tatagaacac tgctacgaag ttctgaatgt ttttccctca gagaggatca aagaacactg 80101 ctgctagtgt ctgaaatttt gatgatcacg taggattcca gaactctcct gctgtggtct 80161 gtatgtttgt ctctcacata ggattccaga acactgctac gagggtctga atgtttgtcc 80221 ctcacaaagg attctagaac actgctgctg ggttctgagt gattgtccct cacataggat 80281 tccagaacac tgctgctggg ttctgagtgt ttgtccctca cataggattc cagaacactg 80341 ctacaagggt ctgaatgttt atccctcaca aagggttcca gaacactgtt actggattct 80401 gagtgtttgt ccctcatatt ggattccaga acaatgctac gagggtctga atatttttcc 80461 ctcacatagg attcgaaaac actcttacga gggtgtgaat gtttttccct cccaaaggaa 80521 tccagaacac tgctgctggg ctctgaatgt ttgtccctca tataggattc cagaacactg 80581 ctacgaggat ctgaatgttt tcccttacaa aggattgtag aacactgcta ctgggttctg 80641 tttatttgcc cctcacaaag gattccagag cactgctgca tatttcttag tgtttgcccc 80701 tcacatagga ttccagaaca cttctccaag gttctgaatg tttgccctca gataggattc 80761 cagtacactg gctggattct gagtgtttgt ccctcacata ggattccaga tcactgctac 80821 aggttctgaa tgtttgtccc tcacaaagga ttctagaaca ctgctactgg tttctgagtg 80881 tttgtccctc acaaaggatt ctagaacatg gcttctgggt tctgtgtgtt tgtccctcac 80941 ataggatgcc aaaacactga tgctgggttc tgagtgtttg tccctcacat agcattccag 81001 aacactgctg ctggcttctg agtgtttgtc cctcacatac aattccagaa cactgctacg 81061 aagttctgaa ggtttgtcgc tgacatagga ttccagaaca ctgctgctgg gttctgagtg 81121 tttgtccctc acataggatt ccagaacact gctacaaggg tctgaatgtt tatccctccc 81181 aaaggattcc agaacactgc tgctgggttc tgagtgtttg cccctcaaat aagattccag 81241 aacactgcta tgagggtctg aatgtttttc cctcacatag gattcaaaag actgttacga 81301 gggtctgaat gtttttccct aacaaaggat tgtagaacac tgtcactggg ttctgtttgt 81361 aggtccctcc cataggattc cagaacacta atacgagggt ctgaatgttt gtccctcaca 81421 taggattcca gaacagagct gctgtgtcct gattgcttgt ctctcacaaa ggattccaga 81481 acactgatgc tgggttctga gtgttcgtct atcacatagg attccagaac aaagctgctg 81541 ggtcctgatt gtttgcccct cacaaaagat tacaaaacac tgctacgagg gtctgaatgt 81601 ttgtccctca tataggattc cagatcactg ttgctgggtt ctgagtgttt gtccctcaca 81661 taggattcca gaacactgct gctgggttct tcgtgtttgt acctcatata ggattccaga 81721 gcactgctac aagactctga atgcttgtcc cttacatagg attccagaac actgttttga 81781 gagtctcaat atttgtccct cacaaaagat tgcagacaac tgctgctgag ttctgagagt 81841 ttgtccttca cttaggaatc cactgattct gggttctgaa tatttgtcct tcacatagga 81901 ttccagaaca gtgctgctgg cttctgagtg attgtcccgc acgtaggatt ccagaacact 81961 gttacgaggg tctgaatgtt cttccctcac aaaggcttcc agaacactgc tgctggtttc 82021 tgtttgtttg tccctcacaa aggattccag agcactgctg ctggttattt agtgtttgtt 82081 gcccacatag gattccagat cacttctgcg aaggtctgaa tgtttagccc tgagatagga 82141 ttccagtaca cactggctcg gttctgagtg tttgtaccac acactggatt ccagaacact 82201 gctgctgggt tctgagtgtt tgcccctcac ataggattcc agaaaactgc tatgaggacc 82261 ttaatgtttg tccatcacaa aagattctag aacaatgctg ctggatctga gtgtccctca 82321 cataggataa cagaacactg cttcgagagt ctaaatgttt gtccctcaca aaggattcta 82381 gaacattgct gctggtttct gagtgtttgt cactcacata ggattccaga acactactgc 82441 tgagttctga ggctttgtat ctcacatagt atttcagaac actgctatga ggttctgaat 82501 gtttgaccct cacagagcat tgcagaacag ggctatgggg atctgaatgc ttgtccctca 82561 catatgaatc cagaacactg ctgcagggtt cagagtgttt atcccacaca taggattaca 82621 gagcactgtt ctgagcatct gagtgtttga ccctcacaaa ggattgcaga acactgctgc 82681 tgggctctga gtgtttgtcc cttacatagg attctagaac actgctgctg ggttctgagt 82741 gtttgtctct cacataggat tccagaacac ttctctgagg atctgaatgt ttgtccctca 82801 caaaacattc cagaacactg ctgctgggtt ctgagtgttt gtccatcaaa taggattcca 82861 gaacacggct gatgggctct gtttgtttgt ccctcacaaa ggattccaga gcactgctgc 82921 tggtttctga atgtttgtcc ctcacatagg attccagaac acttctacga ggctccgaat 82981 gtttgtcctt cagataggat tccagaacac agtggatgtg tgatgagtgt ttgtccctca 83041 aataggattc cacaacactg ctttgagggt ctgaatgttt gtatctcaca aaccagtcta 83101 aaacactact tctgggttct gagtgtttgt ccctcacata gaattctaga acactgcagc 83161 tcgtttctga gtgtttctcc gtcactttgg attccagaac actgctaaga ttgtctgaat 83221 gttcgtccct taccaaatat tccagaacag tgctgctggg ttctgagtgt ttggccctca 83281 cattggtttc cagaacactg ctgtgattgt ctgaatgttt gtccctcaca aattattcca 83341 gagtactgct gctgggttct gagggtttgt ctctcacata gaattaaaga atactgctgc 83401 tgagttctga gattttgtac ctcacatatg attccagaac actgctatga gggtctgaat 83461 atttgttcct cacagagcat tccagaatgg tgctatgagg gtctgaatgc ttgtccctca 83521 cataggcagg gttctgagtg tttgtccctc acacaggact ccagaacact gctctgagag 83581 tctgagtgtt tgaccctcac aaaggattcc agaacactgc tgctgggttc tgagtgtttg 83641 tcccacacat aggattccag aacactgctg ctgctttctt agtgtttgtc tctcacatag 83701 gattccagaa cactgctgcg aggatctgaa tgttgtccct cacaaaggat tagagaacac 83761 tgctgctgag ttctgagtgt ttgtccctct cattggattc cagaacactg ctgctaggtt 83821 ctgagggttt gtccctcaca taggattcca gaacactgct gctggtttct tgggtttgtc 83881 tctcacatag gattgcagaa cactgctacg attatctgaa tgttgtccct cacaaagtat 83941 tacagagcac tgctgctggg ttctctctgt ttgcccctca cattggatta cagaacactg 84001 ctgctaggtt tgagggtttg tccctcacat aggattccaa aacactgttg ctgggttctg 84061 agtgtttgtc cctaacatac gattccagaa cactgctatg attgtctgaa tgtttgtccc 84121 tcacaaagta ttccagagca ctcctcctgg gttaagagtg tttgcccttc acataggatt 84181 ccagaacagt gctgctgggt tctaagtgtt tgtccctcac ataggattcc agaacactgc 84241 tacgaggatc tgaatgtttg tccctcacaa attattccag agtactgctg ctgggttctg 84301 agtgtttgtc cctcacatag gattccagaa cactgatacg aaggtctgaa tgtttgtccc 84361 tcagatagga ttacagaaca cagctacgag gttctgaatg attgtccctc acataggatt 84421 ccagaacaca gtggctgggt tctgagtgtt tgtccctcat ataggatttc agaacactgc 84481 tatgaatttc tgaatgtttg tcgctcacag aggattctag aactctgcgg ctgggttgtg 84541 ttttcccccc acataggatt ccagaatact gctgctgggt tctgagtgtt tgtccctcac 84601 ataggattcc agaactctcc tgctgggttc tgtttgttta cccctcacaa aggaatccac 84661 agcactgttg ctggtttctg agtgtttgtc cctcactcag gataccagaa cactgctacg 84721 atggtctgaa tgtttgtccg tcacaaagga ttcataacac tgctatgggt tctgactgtt 84781 tgtccctcac aatggattcc agaaaactgc tttgagagtc tcaatgtttg tccctcacaa 84841 agtattccag agcactgctg cggggttctg tgtgtttgtc cctcacatgg gattcaaaaa 84901 cactcctgct gggttcagag tgttttccct cacataaaat tccagaacac tactacaagg 84961 ttctgaatgt ttgtccctca cataggattc cagaacactg ctgctgggtt tcgagtgttt 85021 ctccctcaca taggattcca gaacactgct gctcggttct gagtgtttgt ccctcacata 85081 gcattccaga acacaggtac gaagttctga atgtttgtag ctcaagtagg attccagaac 85141 aatgctgctg ggttctgaat gtttgacact cacacaggat tccagaacac tgctgctggg 85201 ttctgagtgt ttgtccctca cataggattc cagaacactg cttcgagggt ctgaatgttt 85261 ttccctcaca aaggactcca gaacactgtt gctgggttct gagtgtttgc ccctcatata 85321 ggattccaga acaatgctac gagtatctga atgtttttcc ctcacatagg attccagaac 85381 attgctacga gggtctgaat gtttttccct cacagagtat tccagaacac tgctgctggg 85441 ttctgaatgt ttgtccctca cataggattc cagaacactg cagctgggtt ctgagtgttt 85501 gtccctcact ttggattcca gaaaacgtct acgacggtct gaatttttgt ccatcacaaa 85561 ggattttaga acactgctgc tggatctgag tgtttgtccc tcacacagga ttccagaaca 85621 ctgcttcgat ggtctgaatg tttgtccctc acaaaggatt ctagaacact gctgctggtt 85681 tcttagtgtt tgtcactcac ataggattcc agaacactgc tgctgggttc tgagtgtttg 85741 tcctcacata cgattccaga acactgctat gaggttctga atgtttgtcc ctcacaaagg 85801 attccagaac actgcttctg agttctgagt gtttgtctgt caaataggat tccagaacac 85861 tgctgctggg ctctgtttgt ttgtccatca caaaggattc cagaacactg ctataggttt 85921 ctgagtgttt gtccctcaca taggattcca gaacaattct acgaggctcc gaatgtttgt 85981 ccttcagata ggatttcaga acacagtggc tgggttctga gtgtttgtcc ctcacatagg 86041 gtatcagaac actgctgctg ggatctgagc gtttgtcttt cacagaggat tccagaacac 86101 tgctgctttg ttctgagtgt ttgtccctca cataggattc cagaacactg ccgctcggta 86161 ctgagggttt gtcccttaca tagaattcta gaacactgca gctcatttct gagtgtttgt 86221 ccctcactta ggattccaga acaatgctac gattgtctga atgtttgttc cttaccaagt 86281 attccagaac actgctgctg ggttctgagt gtttggcact cacattggtt tccagaacac 86341 tgctacgagg gtctgaaaat ctcgcacata ggattccaga acactgctaa gatggtctga 86401 atgtttttcc ctcagaaagg attctggaac cctgctactg gattctgttt gtttgtctct 86461 tacaaaggat ttcagagcac tgctcctggt tgctgagtgt ttgtccctca caaaggattt 86521 cagagcactg ctcctggttg ctgagtgttt gtccctcaca taggattcca gaacacttct 86581 acgagtgtct gaatgtttgt ccctcagata ggattccaga agacagtgga tgggttctgg 86641 gtgtttgtcc atcacatagg attccagaac actgctgctg ggttctgagt gtttgtccct 86701 cacataaggt tccagaacac tgcttctgag tgtttgtccc tcacatagga tcccagaaca 86761 ctgttgctgg gttctgagta tttgtccctc tcatgggatt ccggaaacct gctgctgagt 86821 tcagagtgtt tttccctcac ataggattcc agaacactgc tgctgggttc tgagtgtttg 86881 tccctcacat tggattccag aacactgctg ctgggttttg agtgtttgtc cctcacatag 86941 aattc

An exemplary human KRT8P8 nucleic acid sequence is set forth below (SEQ ID NO: 168; GenBank Accession No: NG_009749.1, Version 1, incorporated herein by reference):

   1 acccacagaa tcaaaaaact cagtgaatca taaacaggat aaataaaaag aaaaccacac   61 ctaggcacat catagtcaag ttgttaaaaa aaacaaagag accaagaagc agcttctctg  121 ctccttctgg aatctctgcc tggttcagcc cacctgcctc cactcctgcc tccaccatgt  181 ccatcagggt gacccagaag tcgtacaagg tgtccacctc tggcacacgg gccttcagca  241 gccgcttcta cacgagtggg cccggtgccc gcatcagctt ctccagcttc tcccgagtgg  301 gcagcagcag cttctggggt ggcctgggcg gaggctatgg tggggccagc ggcatcggag  361 gcatcaccgc cgtcatggtc aaccagagtc tgctgagccg ccttaacctg gaggtggacc  421 ccaacatcca ggccgtgcgc acccaggaga aggagcatat caagacccta ggcaaatttg  481 tctccttcat cgacaaggta ccgttcctgg agcagcagaa caagatgctg gagaccaagt  541 ggagcctcct gcagcagcag gagatggctc agagcaacat ggacaacatg ttcgagagct  601 acatcaacaa ccttaggcgg cagctggaga ctctgggcca ggagaagctg aagctggaga  661 cggagcttgg caacattcag gggctggtgg aggacttcaa ggacgagaat gaggatgaga  721 tcaatatgcg taaagagatg gcaaatgaat ttgtcctcct caagaaggat gtggatgaag  781 ctgacatgaa caaggtagag ctggagtctc gcctggacgg gctgactgac gagatcaact  841 tcctcaggca gctgtatgaa gaggagatcc gggagctgca ttcccagatc tcggatacgt  901 ctgtggtgct gtccgtggac aacagccctc cctggacatg gaaagcatca tcgctgaggt  961 caaggcgtag tacgaggtga tcgccaaccg cagcctggct gaggctgaga gcatggacca 1021 ggtcaagtat gaggagctgc aggtgctggc tgggaagcag ggggatgacc tgcggcatac 1081 agactgagat ctccgagatg aaccggaaca tcagctggct ccaggctgag actgagggcc 1141 tcaaaggccg gatggcttcc ctgtggaggc cgccatcgca gatgccgagc agcttgggga 1201 gctggccgtt aaggatgcta acgtcaagct gtccgagctg gaggccaccc tgcagcgggc 1261 caagcaggac atggcgaggc ggctgcgtga gtaccaggag ctgatgaacg tcaagctagc 1321 cctggacatc gagatcgcca cctacgggaa gctgctggag ggcgaagaga gccagctaga 1381 gtctgggatg cagaacatga gtattcatat gaagaccacc agcggttttg caggtggtct 1441 gagctcggcc tatgggggcc tcacaagccc cggcctcagc tacggcctgg gctccagctc 1501 tggctctggc gcgggcttca gctccttcag ccgcaccagc tccaccaggg ccccggttgt 1561 gaagaagatc gagacccgcg atgggaagct ggtgtccgcg tcctctgacg tcccgcccaa 1621 gtgaacagct gcggcagccc ctcccaccct gcccctcctg cgacttgccc agagcccggg 1681 agggaggccg ctgtgcaggg gagcacaggg aacagaagac acacctgagg ctcggctcta 1741 gccctcagcc caccctcggc ggaattcact gcctgaggac cacccttgcc catgcctcca 1801 actacaaaac aattcaattg cttt

An exemplary human miR218-1 nucleic acid sequence is set forth below (SEQ ID NO: 169; GenBank Accession No: NR_029631.1, Version 1, incorporated herein by reference):

 1 gtgataatgt agcgagattt tctgttgtgc ttgatctaac catgtggttg cgaggtatga 61 gtaaaacatg gttccgtcaa gcaccatgga acgtcacgca gctttctaca

An exemplary human XIST nucleic acid sequence is set forth below (SEQ ID NO: 170; GenBank Accession No: U50908.1, Version 1, incorporated herein by reference):

   1 aagcttggct cccttgaggt taggaattcg ataccagcct ggcaagcatg gtgaaccccg   61 tctctgctaa aaatacaaaa attagccagg catggtggca cacgcctgta atcccagcta  121 ctcgggaggc tgaggcagga gaatcacttg aacccgggag gcagtggttg tagtgagccg  181 agattgtgcc actgcactct ggcctgggct acagagtgag actctgcctc aaacaaaaaa  241 caatcaaaca aaaaccaaat agcaaacaga tatatgaaaa agtgctcaat atcaataatc  301 atcacaaaaa tgcacatcag gctgggtgtg gtggctcaca cctataatcc cagcactttg  361 ggaggccaaa gcgggtggat cacttgaggt caggagttca agaccagcct gcccaatata  421 gtgaaacatc ttctctgcta aaaatacaaa aattagctgg gcatggtggt gggtgcctgt  481 aatcccaccc gctcaggagg ctgaggcagg aggatcactt gaacccggga ggcagaggtt  541 gcaatgagcc gagatggcac cactgcacgg gctgtaacct gggcaacaga atgaggctgt  601 gtctgaaaac agaaataaat aaggccaggc gcagtggttc acatctgtaa tcccagtgtg  661 attacagatc acactgtggg aggccaaggc aggcagatca cctgagctca ggagtttgag  721 accagcctgg tcaacatggt gaacccccgt ctctattaaa aatatacaaa ttagctgggc  781 atggtggcag atgcctataa tccaagctac ttgggaggct gaggcatgag aattgcttga  841 acccaagaag tggaggttgc agtgaaccgt gatcacacca ctgcactcca gccttggcga  901 cagagagaga ttctgtctca aaaaaataaa aattaaaaaa aaaaaagaaa gaaagaaaaa  961 aaaaagaaaa atgcaaatca aaaccacaat gcaatattgc ctcacacctg ttagaatggc 1021 tattttcaag aagacaaaag ttaaggattg gtgagggtgt ggagaaaagg gaacatttat 1081 acagtgttgg tggaaatata aattagttca accatcatgg aggcttctga aaacactaaa 1141 aatacaacta ccttatgatc caataatccc acttgtgggt gttgttcaaa gaaattgaaa 1201 tcagtgtgtt gaagagacat ttgtcctcct atgtttatta tagcattatt cacaatagtc 1261 aagatatgaa atcaaggtaa gtccccatca acagatgaat gtataaagaa aatgtggtat 1321 acatacacaa tggaacacta gtcagcctta aaaagaagga aaatctgtca tttgcaacaa 1381 catatatgaa cctggaggac attatgctaa gccaggcaca gaaagatgaa tactatatta 1441 tctcacttgt atgtgtaatt ttcaaaactt gaacttgtag ggagtagact ggtggttaat 1501 aatctgaagg gagggtaaaa atgtgttgat caaaggataa aaattttagt tagagagaag 1561 gaataagttt ttgagatata ttgcagagca tgatgacaat agtgataagg tattgtacat 1621 ttcaaaaact gctaagtaaa ttttaagtat tctcatcaca aaataagtat gtgagctgag 1681 atatatagta attagcttga tttaattatt ctacaatgca tgcatatatc aaaataccac 1741 attttactcc atgaatatat acaattattt gtgaactaaa aatacatttt gaaaaagaac 1801 tactagaaaa actaaaaatg agaaaataaa taagcacatt aattaattaa ttaaaatcct 1861 tgtctagtaa gtttaatgtt ggtactttct cagggaccat tttttgttaa ttaccttttt 1921 ttctatatat tagctataat ttcctgtttt ttgtatgcct tgtaattttt aataaaaatg 1981 aacagtttta atattataat gtgatacctt gggaaataaa attcctccct ctccctagtg 2041 tttgctggtg attttttttt ttttttttga gatggagtct tgctctgtca ccaggcttgg 2101 cgcggtctca gctcactgca acctccgcct tccgggttca agcgattctc ctgcctcagc 2161 ctcccgagta gctgggatta caggcgtgtg ccaccatgtg cagcttattt ttgtatttat 2221 agtagagatg gggtttcacc atattgacca ggatggtctt gatttcctga cctcatgatc 2281 tgtctgcctc gcctccaagt gctggattac agcatgagcc accgcacccg ccactggtga 2341 tgttttaata gattgtaatt tttttgaggt agcgtttgct ttctcaccca gtctggagtt 2401 cagtgggcca atcacaagcc cactgtatcc ttgaactact gggctcaatc aatcctcctg 2461 cttcatcctc ctgagaagct agaactacgg gtatgcacca ccacgcctgg ctaattttta 2521 tattttttat ttttgtagag acagaggtct ctctattttg cccaggctga tctcgaactc 2581 ctggcctcaa aagatcctcc tgccttggcc tcctaaagtg ctgagattaa aggtgtgagc 2641 caacgtaccc agcccattta cagtattttt aatgttgacg tgagctatgt atacaattgt 2701 taagcatata ctcactgagc tttaatatgt ataaccccgt gttctctttt gataaactag 2761 aaaacctttc ccaacatcct aatacacttt tgaaggatat cataaatagt gtgtttgagg 2821 gctagaggaa tggcccaagt actgtgatga ggttcatagg atttggggct atttggaaga 2881 cccttacaag gcatatagca caacttttct atctgttgat tgtctctgta gcatcctcac 2941 aaaatccact attggcttgc aggtcttcag agactggcat tcaccagttc tggaggtgtt 3001 aactgttcca tctttggaca gctcagagta ttcagacgtc tttatttatt agaactacac 3061 acaacaggac tattcatcaa cttcccccat tgcagacagc cctttgagtt gtaaagagcc 3121 cttccccagg tcttttattt tcttttccat aatatgtcct ggtcccttta actgcttttc 3181 actggtgatg atttggaggg cccccaccag cctgctaatt agatcctgaa ggctttatca 3241 aagtcctctt taaatggcat agccctgaag ccaaggacag actcctgttt agtgggggga 3301 ggggctcttc aaattagagg gggttgagca cttttctttg accctttctt ctgatactga 3361 ccttgtatga atcagacttt ccccccttta tatcagattc tggtcctgcc ctgtatacaa 3421 ctttggctcc tttcctgcag acaggctcag tgcttctttg gtgattttat gctgccatct 3481 ggtggctaag tcgacagtgc cggctttttt tgggcctaat ttagcagagg agaggatgta 3541 cagatgaaca tagtgacaat cctagaactg gaataatctg aatctttaaa aagaggacct 3601 gatttcttcc tattgtgtgc catgtgattg ggagcccaaa gaagaggatg ctaacacagc 3661 tatggcatgg ccacagaaaa tatgcctgaa atatccccat cagagcccaa ctcttactag 3721 ctaattgact ttgagcaagt cacttttcct tctagtgtct cagtttccat acttctgatc 3781 ctaacaggtt tataaaatgg agccaagcag tagtgaaggt gaggccaggt cgggaagagg 3841 aggaagtaaa gtgaattgaa agctagtgag ggcaggggag taagtaaaac ctgaaggtga 3901 taaatggcag aagagggcag gactgctcta gggcaaaggc ctaggcaaat atttttcaga 3961 agttcctttt aatgtaaaca gtttgattaa aaatatatta caaatacatg ggcccatgtg 4021 aggtgtagtg atttatcaat gaaaatttag aataccaggt ggagaagaga tgcttacgta 4081 tttgtttatt caacagttca catatcaatt tttataatga ccttgcacca tatcttcctt 4141 tttaggtcca gaaatcatct ctttgtgttt attgtcaaat gcaccattcc tggctaattt 4201 cacatctccc tctatgagaa aaacatagca acactgtact acttccattt ttgcaatggc 4261 actctggaac ctctttgtat tgaaattata aatttcttgc ttttgcagtt tctttagcct 4321 aagggtcaac agtggattta ggtaggccac agctctgaac atgtcctgtg tccaatgtga 4381 gtgtcacccc ataacggcac atcagcacca ttttgcatgc ctagccttaa gagttaccat 4441 ttaaaaaact ccaatgacaa ccaatgagag tgatctgcta gcgtggctgc ccacctggaa 4501 ccagggcctg gtcacagaaa cccaggacaa ccagtttata aattgtcttt ttggcttttt 4561 atttgaaaag gtatttttgt gaaacaaaag gttttaattt cagagtcaaa tttatcaatc 4621 tttcatattt gatgctactt gagtctttag aaaatttttc cccaactaaa tttctttttt 4681 ctttttttga gatggagtct tggtctgtcg cccgggctgg agcgcagtgg caccatctcg 4741 gttcactgca acctccgcct cctggattca agtgattctc ctgcctcagc ctcccaagta 4801 gctgggatta taggtgcctg ccaccatgcc cggctaattt ttgtatttat agtagagacg 4861 gggtttcgct atgttggcca ggctggtctc aaactcctca cctcaggtga tccagccacc 4921 tcggcctccc aaagtgctgg gattacaagc atgagccacc gcgcccggcc aaccaaattt 4981 cttaaaagta tagaacattt ccacacttgt agaaacttct agtagataaa gttgtattag 5041 aggtttggta atccagtctt tctgatagct gcttcatagg tgtcactgta ggtagtttct 5101 ctctttgtta agcattgttt tcctcaaagg taccattgta ttgcaccact ttacaataca 5161 ataaccctca tttggaatga caagtcagat tacttttttt gtttgatcca aggacactta 5221 gaagatggaa ggtatttctt aaggaagaaa atttgcatac tttattattt ttctggaaac 5281 tgaagagcaa gcttacctga tagatttggg tcgatagtta cactttccag ttcagccagt 5341 gggagggtaa tgtatccttt gactttctag aagttgctct ataatactta agttgccatt 5401 gtctcccttc tggttctctg ttgtttctcg aatgacatag aagagtttat gagattaatt 5461 gcttcctact gaaatagcca ggtttctgag ggcagctttg gcttttatat gagctttttc 5521 ttcctaccac ttatcagtta ctgacagagg gtcaacttca ctactgtgtc atatggttgg 5581 tccaatgttg ggttcctcag attcatggag gaaataggaa aatagtaaag attaaggagt 5641 catagttaaa aaattacaaa caggtcacaa accagtactc tttcttgatt atttaggaac 5701 caaatagcca ttctatgaaa tgtcttcctt tcctttttct ctcttgctca ccaattgact 5761 cgtaagcact tccgttctct tatggttggg agccatacaa ggtagagtgt tggagtaaaa 5821 actacattga ctctgaatca tggtgtgtga cctcgggcac atgatgtaac ctctatagga 5881 ctctatttta atgtataaaa caggaataat cctttattat tatctatgca atacatattc 5941 cattatctat tacatgggat aatggaatgg gaagtccctt gaagatggta ctaacctcaa 6001 tgtattactc ctttctagct tctttgggtc aaaagtttgg tggaggagtt acaaattctg 6061 gtttgaatga tatatttgga tactttatca acacatcaaa gctctaccta tcccttcccc 6121 cattctcaaa accaagctga attaacatct ttacatttat tatgcagttt atggaggatt 6181 ttagcattaa ttattgcttg atttactcaa tgtccccatg ttatagatga gaactggaaa 6241 acccattgaa gttgtgactc ctggtctaga aatgaagtct acttccagtt aatgttcttt 6301 ctggtatgtc tttgctttct tgaaatttcc cttttttgtc cttactgggt aaattttgaa 6361 ccaaccaaat cacaaagatg tccggctttc aatcttctag gccacgcctc ttatgctctc 6421 tccgccctca gccccccctt cagttcttaa agcgctgcaa ttcgctgctg cagccatatt 6481 tcttactctc tcggggctgg aagctt

An exemplary human PSG10P nucleic acid sequence is set forth below (SEQ ID NO: 171; GenBank Accession No: NR_026824.1, Version 1, incorporated herein by reference):

   1 gcagaaggag gaaggacagc acagcctaca gccgtgctca ggaagtttct ggaacctagg   61 ctcatctcca cagaggagaa cacacaagca gcagagacca tggggcccct ctcagcccct  121 ccctgcacac agcacatcaa atggaagggg gtcctgctca cagcatcact tttaaacttc  181 tggaacccac ctaccattgc ccaagtcacg actgaagccc agccacccaa agtttccgag  241 gggaaggatg ttcttctact tgtccacaat ttgccccaga atcttactgg ttacatgtgg  301 tagaaagggc aaataaggga cctctaccat tacattacat catatgtagt agacggtcaa  361 agaattacat atgggcctgc atacagtgga cgagaaacag tatattccaa tgcatccctg  421 ctgatccaga atgtcacccg ggaggacgga gtatcctaca ccttacacat catacagcga  481 ggtgatggga ctagaggagt aactggaaat ttcaccttca ccttataccc gaagctgccc  541 aagccctaca tcaccatcaa caactcaaaa cccagggaga ataaggatgt cttacccttc  601 acctgtgacc ctaaaagtga gaactacacc tacacgtggt ggctaaatgg tcagagcctc  661 ccagtcagtc ccagggtaaa gtgacccatt gaaaacagga tcctcattct acccagtgtc  721 acgagaaatg aaacaggacc ctatcaatgt gaaatacggg accgatatgg tggcatccgc  781 agtaacccag tcaccctgaa tgtcctctat ggtccagacc tccccagaat ttacccttca  841 ttcacctatt accgttcagg acaaaacctt tacttgtcct gcttcgcgga atgtaaccca  901 ccggcatagt actcttggac aattaatggg aagtttcagc aatcagaaca aaagctcttt  961 atcccccaaa ttactacaaa gcatagaggg ctctatgctt gctctgttcg taactcagcc 1021 actggcaagg aaagctccaa atccatgaca gtcgaagtct ctggtgcctg ccatggagac 1081 ctggcagggt ctcattcgtg actgccataa cagagacact gagaaaaaga tgcaaccatg 1141 gaaaggtgca aaggtggcaa gttctaatga catagaaaat agcaatcagc ctttctcaca 1201 tctgaaagcc ttccaaaata tctgagtgca gtagagaatt gacagaggac tgatcaccaa 1261 cctagaagta tgctcctcca ggaataggac gtcttccttt ctttactcca atagagcagc 1321 ggtgatgtca tttctgtatt tcaggaagac tggcaggaga tttatggaaa agactctgac 1381 aaggactctg gaatacaagc tcctgataac ttcaagatca taccactgga ctaagaactt 1441 tcaaaatttt aatgaacagg ctgatacctt catgaaattc aagacaaaga agaaaaaaaa 1501 ctcaatttta ttggaataaa taatcaaaag gataatgttt tcataatttt ctatttgaaa 1561 atgtgctgag tctttgaatg ttttattctc cagatttatg aacttttttc cttgaacaat 1621 tggtaaagta tacttttgta aacaaaaatt gaaacatttg cttttgctga gtgccccaga 1681 attgggaaac tattcatgag tattcatatg tttatggtaa taaagttatt tgcacaactt 1741 ca

An exemplary human miR1262 nucleic acid sequence is set forth below (SEQ ID NO: 172; GenBank Accession No: NR_031664.1, Version 1, incorporated herein by reference):

 1 atctacaatg gtgatgggtg aatttgtaga aggatgaaag tcaaagaatc cttctgggaa 61 ctaatttttg gccttcaaca agaattgtga tat

An exemplary human RP11-360D2.1 nucleic acid sequence is set forth below (SEQ ID NO: 173; GenBank Accession No: HG492934.1, Version 1, incorporated herein by reference):

  1 agctgtcttc ttcgtcttat ttgttttgtc tgtgcattac ctgtggaaga aatggaagaa  61 acaccaaaaa aagctgaaaa agcaagcctc cttagaaaaa cctggtaatg atctagaaag 121 cccattgatc aacaacattg accaaacact ccacagagtg gcaaccacag catcagtgat 181 atacaagatc tgggagcaca ggtctcacca tccttcctct aagaaaatta agcactgcaa 241 attaaagaag aagagtaaag aagaaggagc cagaagatac taaataaatg catatgcaaa 301 tgtagcttag tcaattatag atatcacaaa agaaatctat catctaagga ttaaaaattg 361 ttctttggaa acctttataa a

An exemplary human RP11 amino acid sequence is set forth below (SEQ ID NO: 174; GenBank Accession No: NP_056444.3, Version 3, incorporated herein by reference):

  1 msladellad leeaaeeeeg gsygeeeeep aiedvqeetq ldlsgdsvkt iaklwdskmf  61 aeimmkieey iskqakasev mgpveaapey rvivdannit veienelnii hkfirdkysk 121 rfpeleslvp naldyirtvk elgnsldkck nnenlqqilt natimvvsvt asttqgqqls 181 eeelerleea cdmalelnas khriyeyves rmsfiapnls iiigastaak imgvaggltn 241 lskmpacnim llgagrktls gfsstsvlph tgyiyhsdiv qslppdlrrk aarlvaakct 301 laarvdsfhe stegkvgyel kdeierkfdk wgepppvkqv kplpapldgq rkkrggrryr 361 kmkerlglte irkganrmsf geieedayqe dlgfslghlg ksgsgrvrqt qvneatkari 421 sktlqrtlqk qsvvyggkst irdrssgtas svaftplqgl eivnpqaaek kvaeanqkyf 481 ssmaeflkvk geksglmst

An exemplary human RP11 nucleic acid sequence is set forth below (SEQ ID NO: 175; GenBank Accession No: NM_015629.3, Version 3, incorporated herein by reference):

   1 tagtttcctg tttccggctt cgcttcggcc cacccccacg tccaccccga atccctgctt   61 aaaggccttg ctttcttgtc taacgccgca accagtcctc tgagttgcca acgtctttct  121 tcttgtctcg acgccccgtc gtccggccac agcgattctc tgcttagcag gatcggtcca  181 cagcgggacg tgagtccctt tcctcctcgc ggcttaccgc ctctctccgc ctagtgccag  241 gtgctaataa agttgttgtt tcaaatgcgg ccaggaacat cgcgagcggg gaccaatcag  301 agagtagctt tgcctctata acggcgcgag agtgagacgt catcggtgag cgactaacgc  361 tagaaacagt ggtgcgcgga gaggagaggc ctcgggatgt ctctggcaga tgagctctta  421 gctgatctcg aagaggcagc agaagaggag gaaggaggaa gctatgggga ggaagaagag  481 gagccagcga tcgaggatgt gcaggaggag acacagctgg atctttccgg ggattcagtc  541 aagaccatcg ccaagctatg ggatagtaag atgtttgctg agattatgat gaagattgag  601 gagtatatca gcaagcaagc caaagcttca gaagtgatgg gaccagtgga ggccgcgcct  661 gaataccgcg tcatcgtgga tgccaacaac ctgaccgtgg agatcgaaaa cgagctgaac  721 atcatccata agttcatccg ggataagtac tcaaagagat tccctgaact ggagtccttg  781 gtccccaatg cactggatta catccgcacg gtcaaggagc tgggcaacag cctggacaag  841 tgcaagaaca atgagaacct gcagcagatc ctcaccaatg ccaccatcat ggtcgtcagc  901 gtcaccgcct ccaccaccca ggggcagcag ctgtcggagg aggagctgga gcggctggag  961 gaggcctgcg acatggcgct ggagctgaac gcctccaagc accgcatcta cgagtatgtg 1021 gagtcccgga tgtccttcat cgcacccaac ctgtccatca ttatcggggc atccacggcc 1081 gccaagatca tgggtgtggc cggcggcctg accaacctct ccaagatgcc cgcctgcaac 1141 atcatgctgc tcggggccca gcgcaagacg ctgtcgggct tctcgtctac ctcagtgctg 1201 ccccacaccg gctacatcta ccacagtgac atcgtgcagt ccctgccacc ggatctgcgg 1261 cggaaagcgg cccggctggt ggccgccaag tgcacactgg cagcccgtgt ggacagtttc 1321 cacgagagca cagaagggaa ggtgggctac gaactgaagg atgagatcga gcgcaaattc 1381 gacaagtggc aggagccgcc gcctgtgaag caggtgaagc cgctgcctgc gcccctggat 1441 ggacagcgga agaagcgagg cggccgcagg taccgcaaga tgaaggagcg gctggggctg 1501 acggagatcc ggaagcaggc caaccgtatg agcttcggag agatcgagga ggacgcctac 1561 caggaggacc tgggattcag cctgggccac ctgggcaagt cgggcagtgg gcgtgtgcgg 1621 cagacacagg taaacgaggc caccaaggcc aggatctcca agacgctgca gcggaccctg 1681 cagaagcaga gcgtcgtata tggcgggaag tccaccatcc gcgaccgctc ctcgggcacg 1741 gcctccagcg tggccttcac cccactccag ggcctggaga ttgtgaaccc acaggcggca 1801 gagaagaagg tggctgaggc caaccagaag tatttctcca gcatggctga gttcctcaag 1861 gtcaagggcg agaagagtgg ccttatgtcc acctgaatga ctgcgtgtgt ccaaggtggc 1921 ttcccactga agggacacag aggtccagtc cttctgaagg gctaggatcg ggttctggca 1981 gggagaacct gccctgccac tggccccatt gctgggactg cccagggagg aggccttgga 2041 agagtccggc ctggcctccc ccaggaccga gatcaccgcc cagtatgggc tagagcaggt 2101 cttcatcatg ccttgtcttt tttaactgag aaaggagatt ttttgaaaag agtacaatta 2161 aaaggacatt gtcaagatct gtcaaaaaaa aaaaaaaaaa a

An exemplary human RP1 amino acid sequence is set forth below (SEQ ID NO: 176; GenBank Accession No: AAA20120.1, Version 1, incorporated herein by reference):

  1 mqkwfsafdd aiiqrqwran psrggggvsf tkevdtnvat gapprrqrvp gracpwrepi  61 rgrrgarpgg gdaggtpget vrhcsapedp ifrfsslhsy pfpgtiksrd mswkrhhlip 121 etfgvkrrrk rgpvesdplr gepgsaraav selmqlfprg lfedalppiv lrsqvyslvp 181 drtvadrqlk elgeggeiri vglgfdldah giiftedyrt rvlkacdgrp yagavqkfla 241 svlpacgdls fqqdqmtqtf gfrdseithl vnagvltvrd agswwlavpg agrfikyfvk 301 grqavlsmvr kakyrellls ellgrrapvv vrlgltyhvh dligaqlvdc isttsgtllr 361 lpet

An exemplary human RP1 nucleic acid sequence is set forth below (SEQ ID NO: 177; GenBank Accession No: NM_006269.1, Version 1, incorporated herein by reference):

   1 gacatactga gaataaatcc aaagacatta gtttctttgc acgaaatgag gttacatatc   61 cagtgacatt tatttgagct atttaaacaa cttaaacatc tttttctttt cttaataagg  121 gacgtttcaa gttgtggtct cagccaaaat gagtgatacc ccttctactg gtttttccat  181 cattcatcct acgtcttctg aaggtcaagt tccaccccct cgccatttga gcctcactca  241 tcctgttgtg gccaagcgaa tcagtttcta caagagcgga gacccccaat tcggcggggt  301 cagggtggtg gtcaaccctc gctcctttaa gtcctttgat gctctgctgg ataacttgtc  361 caggaaggtg cccctccctt ttggagtgag gaacatcagc acccctcggg gcaggcacag  421 catcacgcgc ctggaggagc tggaggacgg cgagtcctac ctatgttccc acggcaggaa  481 ggtgcagcct gtagacctgg acaaagcccg tcggcgcccg cggccctggc tcagcagccg  541 ggccattagc gcgcactcac cgccccaccc cgtagccgtc gctgctcccg gcatgccccg  601 ccccccacgg agcctagtgg tcttcaggaa tggcgacccg aagacgaggc gtgcggttct  661 tctgagcagg agggtcaccc agagcttcga ggcatttcta cagcacctga cagaggtcat  721 gcagcgccct gtggtcaagc tgtacgctac ggacggaagg agggttccca gcctccaggc  781 agtgatcctg agctctggag ctgtggtggc ggcaggaagg gagccattta aaccaggaaa  841 ttatgacatc caaaaatact tgcttcctgc tagattacca gggatctctc agcgtgtgta  901 ccccaaggga aatgcaaagt cagaaagcag aaagataagc acacatatgt cttcaagctc  961 aaggtcccag atttattctg tttcttctga gaaaacacat aataatgatt gctacttaga 1021 ctattctttt gttcctgaaa agtacttggc cttagaaaag aatgattctc agaatttacc 1081 aatatatcct tctgaagatg atattgagaa atcaattatt tttaatcaag acggcactat 1141 gacagttgag atgaaagttc gattcagaat aaaagaggaa gaaaccataa aatggacaac 1201 tactgtcagt aaaactggtc cttctaataa tgatgaaaag agtgagatga gttttccagg 1261 aagaacagaa agtcgatcat ctggtttaaa gcttgcagca tgttcattct ctgcagatgt 1321 gtcacctatg gagcgaagca gtaatcaaga gggcagtttg gcagaggaga taaacattca 1381 aatgacagat caagtggctg aaacttgcag ttctgctagt tgggagaatg ctactgtgga 1441 cacagatatc atccagggaa ctcaagacca agcaaagcat cgtttttata ggccccctac 1501 acctggacta agaagagtga gacaaaagaa atctgtgatt ggcagtgtga ccttagtatc 1561 tgaaactgag gttcaagaga aaatgattgg acagttttca tatagtgaag aaagggaaag 1621 tggggaaaac aagtctgagt atcacatgtt tacacattct tgcagtaaaa tgtcatcagt 1681 atctaacaaa ccagtacttg ttcagatcaa taacaatgat caaatggagg agtcatcatt 1741 agaaagaaaa aaggaaaaca gtctgcttaa gtcaagtgca ataagtgctg gtgttataga 1801 aattacaagt cagaagatgt tagagatgtc acataataat ggtttgccat caactatatc 1861 aaataactca attgtggagg aagatgtagt tgattgtgtg gtattggaca acaaaactgg 1921 tatcaagaac ttcaaaactt atggtaacac caatgatagg ttcagtccta tttcagcaga 1981 tgcaacccat ttttcaagta ataactctgg aactgacaaa aatatttctg aggctccagc 2041 ttcagaagca tcctctactg tcactgcaag aattgacaga ctaattaatg aatttgctca 2101 gtgtggttta acaaaacttc caaaaaatga aaagaagatt ttgtcatctg ttgccagcaa 2161 aaagaagaaa aaatctcgac agcaagcaat aaattccagg tatcaagatg gacagcttgc 2221 aaccaaagga attcttaata agaatgagag aataaacaca aaaggtagaa ttacaaagga 2281 aatgatagtg caagattcag atagtcccct taaaggaggg atactttgtg aggaagacct 2341 ccagaaaagt gatactgtaa ttgaatcaaa tactttttgt tccaaaagta atctcaattc 2401 cacgatttcc aagaatttcc atagaaataa attaaatact actcaaaatt ccaaggttca 2461 aggactttta accaaaagaa aatctagatc actaaataaa ataagcttag gagcacctaa 2521 aaaaagagaa atcggtcaaa gagataaagt gtttcctcac aatgaatcta aatattgcaa 2581 aagtactttt gaaaacaaaa gtttatttca tgtatttaac atccttgagc aaaaacccaa 2641 agatttttat gcaccgcaat ctcaagcaga agtggcatct gggtatttga gaggaatggc 2701 aaagaagagt ttagtttcaa aagttactga ttcacacata actttaaaaa gccagaaaaa 2761 acgtaaaggg gataaagtga aagcaagtgc tattttaagt aaacaacatg ctacaaccag 2821 ggcaaattct ttagcttctt tgaaaaaacc tgattttcct gaggctattg ctcatcattc 2881 aattcaaaat tatatacaga gttggttgca gaacataaat ccatatccaa ctttaaagcc 2941 tataaaatca gctccagtat gtagaaatga aacgagtgtg gtaaattgta gcaataatag 3001 tttttcaggg aatgatcccc atacaaattc tggaaaaata agtaattttg ttatggaaag 3061 taataagcac ataactaaaa ttgccggttt gacaggagat aatctatgta aagagggaga 3121 taagtctttt attgccaatg acactggtga agaagatctc catgagacac aggttggatc 3181 tctgaatgat gcttatttgg ttcccctgca tgaacactgt actttgtcac agtcagctat 3241 taatgatcat aatactaaaa gtcatatagc tgctgaaaaa tcaggaccag agaaaaaact 3301 tgtttaccag gaaataaacc tagctagaaa aaggcaaagt gtagaggctg ccattcaagt 3361 agatcctata gaagaggaaa ctccaaaaga cctcttacca gtcctgatgc ttcaccaatt 3421 gcaagcttca gttcctggta ttcacaagac tcagaatgga gttgttcaaa tgccaggttc 3481 acttgcaggt gttccctttc attctgcaat atgtaattca tccactaatc tccttctagc 3541 ttggctcttg gtgctaaacc taaagggaag tatgaatagc ttctgtcaag ttgatgctca 3601 caaggctacc aacaaatctt cagaaacact tgcattgttg gagattctaa agcacatagc 3661 tatcacagag gaagctgatg acttgaaagc tgctgttgcc aatttagtgg agtcaactac 3721 aagccacttt ggactcagtg agaaagaaca agacatggtt ccaatagatc tttctgcaaa 3781 ttgttccacg gtcaacattc agagtgttcc taagtgcagt gaaaatgaaa gaacacaagg 3841 aatctcctct ttggatggag gttgctctgc cagtgaggca tgtgcccctg aagtctgtgt 3901 tttggaagtg acttgctctc catgtgagat gtgcactgta aataaggctt attctccaaa 3961 agagacatgt aaccccagtg acactttttt tcctagtgat ggttatggtg tggatcagac 4021 ttctatgaat aaggcttgtt tcctaggaga ggtctgttca cttactgata ctgtgttttc 4081 tgataaggct tgtgctcaaa aggagaacca tacctatgag ggagcttgcc caattgatga 4141 gacctacgtt cctgtcaatg tctgcaatac cattgacttt ttaaactcca aagaaaacac 4201 atatactgat aacttggatt caactgaaga gttagaaaga ggtgatgaca ttcagaaaga 4261 tctaaatatt ttgacagacc ctgaatataa aaatggattt aatacattgg tgtcacatca 4321 aaatgtcagt aatttaagct cctgtggcct ttgcctaagt gaaaaagaag cagaacttga 4381 taagaaacat agttctctag atgattttga aaattgttca ctaaggaagt ttcaggatga 4441 aaatgcatat acttcctttg atatggaaga accacggact tctgaagaac caggctcaat 4501 aaccaacagc atgacatcaa gtgaaagaaa catttcagaa ttggaatctt ttgaagaatt 4561 agaaaaccat gacactgata tctttaatac agtggtaaat ggaggagagc aagccactga 4621 agaattaatc caagaagagg tagaggctag taaaacttta gaattgatag acatctctag 4681 taagaatatt atggaagaaa aaagaatgaa cggtataatt tatgaaataa tcagtaagag 4741 gctggcaaca ccaccatctt tagatttttg ctatgattct aagcaaaata gtgaaaagga 4801 gaccaatgaa ggagaaacta agatggtaaa aatgatggtg aaaactatgg aaactggaag 4861 ttattcagag tcctctcctg atttaaaaaa atgcatcaaa agtccagtga cttctgattg 4921 gtcagactat cggcctgaca gtgacagtga gcagccatat aaaacatcca gtgatgatcc 4981 caatgacagt ggcgaactta cccaagagaa agaatataac ataggatttg ttaaaagggc 5041 aatagaaaaa ctgtacggta aagcagatat tatcaaacca tctttttttc ctgggtctac 5101 ccgcaaatct caggtttgtc cttataattc tgtggaattt cagtgttcca ggaaagcaag 5161 tctttatgat tctgaagggc agtcatttgg ctcttctgaa caggtatcta gtagttcatc 5221 tatgttgcag gaattccagg aggaaagaca agataagtgt gatgttagtg ctgtgaggga 5281 caattattgt aggggtgaca ttgtagaacc tggtacaaaa caaaatgatg atagcagaat 5341 cctcacagac atagaggaag gagtactgat tgacaaaggc aaatggcttc tgaaagaaaa 5401 tcatttgcta aggatgtcat ctgaaaatcc tggcatgtgt ggcaatgcag acaccacatc 5461 agtggacacc ctacttgata ataacagcag tgaggtacca tattcacatt ttggtaattt 5521 ggccccaggc ccaacgatgg atgaactctc ctcttcagaa ctcgaggaac tgactcaacc 5581 ccttgaacta aaatgcaatt actttaacat gcctcatggt agtgactcag aaccttttca 5641 tgaggacttg ctggatgttc gcaatgaaac ctgtgccaag gaaagaatag caaatcatca 5701 tacagaggag aagggtagtc atcagtcaga aagagtatgc acatctgtca ctcattcctt 5761 tatttctgct ggtaacaaag tctaccctgt ctctgatgat gctattaaaa accaaccatt 5821 gcctggcagt aatatgattc atggtacact tcaggaagct gactctttgg ataaactgta 5881 tgctctttgt ggtcaacatt gcccaatact aactgttatt atccaaccca tgaatgagga 5941 agaccgagga tttgcatatc gcaaagaatc tgatattgaa aatttcttgg gtttttattt 6001 atggatgaaa atacacccat atttacttca gacagacaaa aatgtgttca gggaagagaa 6061 caataaagca agtatgagac aaaatcttat tgataatgcc attggtgata tatttgatca 6121 gttttatttc agtaacacat ttgacttgat gggtaaaaga agaaaacaaa aaagaattaa 6181 cttcttgggg ttagaggaag aaggtaattt aaagaaattt caaccagatt tgaaggaaag 6241 gttttgtatg aatttcttgc acacatcatt gttagttgtg ggtaatgtgg attcaaatac 6301 acaagacctc agcggtcaga caaatgaaat ctttaaagca gtcgatgaga ataacaactt 6361 attaaataac agattccagg gctcaagaac aaatctcaac caagtagtaa gagaaaatat 6421 caactgtcat tacttctttg aaatgcttgg tcaagcttgc ctcttagata tttgccaagt 6481 tgagacctcc ttaaatatta gcaacagaaa tattttagaa ctttgtatgt ttgagggtga 6541 aaatcttttc atttgggaag aggaagacat attaaattta actgatcttg aaagcagtag 6601 agaacaagaa gatttataat ttcaatatca gcacactcat tctttgtcaa ttcatttttt 6661 cccatgagat gaagcacatg tgacgaatac ggactagata acctctaaga attttccact 6721 tcttcaaaat gaacttactc tagaaagctt acccttggat aaccagtttg actttcataa 6781 tgtctctgtt ttttgttttt ccaacaatta cagactcagg ttctcttatt ttggaagttt 6841 ctatctggtt ttgttctgaa cttacatttt tttttttttt ggtatctatg attttttttg 6901 ctcagggcat caaaatgtgc taaggacaag aattatatcc tttttaaaaa atgttgttag 6961 cttggtgtaa aatgtatatt gactgtattg gtgaataaat tgaatagaca taacctcaaa 7021 gtacttcact tattcttttt aactactgat ttgataaaaa gtatgattat aagatatcca 7081 cgacaatctc atagtttctt

An exemplary human CD28 amino acid sequence is set forth below (SEQ ID NO: 178; GenBank Accession No: AAI12086.1, Version 1, incorporated herein by reference):

1 mlrlllalnl fpsiqvtgnk ilvkqspmlv aydnavnlsc kysynlfsre fraslhkgld 61 savevcvvyg nysqqlqvys ktgfncdgkl gnesvtfylq nlyvnqtdiy fckievmypp 121 pyldneksng tiihvkgkhl cpsplfpgps kpfwvlvvvg gvlacysllv tvafiifwvr 181 skrsrllhsd ymnmtprrpg ptrkhyqpya pprdfaayrs

An exemplary human CD28 nucleic acid sequence is set forth below (SEQ ID NO: 179; GenBank Accession No: AJ295273.1, Version 1, incorporated herein by reference):

1 atgctcaggc tgctcttggc tctcaactta ttcccttcaa ttcaagtaac aggaaacaag 61 attttggtga agcagtcgcc catgcttgta gcgtacgaca atgcggtcaa ccttagctac 121 aatgagaaga gcaatggaac cattatccat gtgaaaggtg aggagtaaga ggagcaggct 181 cctgcacagt gactacatga acatgactcc ccgccgcccc gggcccaccc gcaagcatta 241 ccagccctat gccccaccac gcgacttcgc agcctatcgc tcctga

An exemplary human ICOS amino acid sequence is set forth below (SEQ ID NO: 180; GenBank Accession No: AAH28006.1, Version 1, incorporated herein by reference):

1 mksglwyffl fclrikvltg eingsanyem fifhnggvqi lckypdivqq fkmqllkggq 61 ilcdltktkg sgntvsiksl kfchsqlsnn sysfflynld hshanyyfcn lsifdpppfk 121 vtltggylhi yesqlccqlk fwlpigcaaf vvvcilgcil icwltkkm

An exemplary human ICOS nucleic acid sequence is set forth below (SEQ ID NO: 181; GenBank Accession No: NM_012092.3, Version 3, incorporated herein by reference):

1 cgagagcctg aattcactgt cagctttgaa cactgaacgc gaggactgtt aactgtttct 61 ggcaaacatg aagtcaggcc tctggtattt ctttctcttc tgcttgcgca ttaaagtttt 121 aacaggagaa atcaatggtt ctgccaatta tgagatgttt atatttcaca acggaggtgt 181 acaaatttta tgcaaatatc ctgacattgt ccagcaattt aaaatgcagt tgctgaaagg 241 ggggcaaata ctctgcgatc tcactaagac aaaaggaagt ggaaacacag tgtccattaa 301 gagtctgaaa ttctgccatt ctcagttatc caacaacagt gtctcttttt ttctatacaa 361 cttggaccat tctcatgcca actattactt ctgcaaccta tcaatttttg atcctcctcc 421 ttttaaagta actcttacag gaggatattt gcatatttat gaatcacaac tttgttgcca 481 gctgaagttc tggttaccca taggatgtgc agcctttgtt gtagtctgca ttttgggatg 541 catacttatt tgttggctta caaaaaagaa gtattcatcc agtgtgcacg accctaacgg 601 tgaatacatg ttcatgagag cagtgaacac agccaaaaaa tctagactca cagatgtgac 661 cctataatat ggaactctgg cacccaggca tgaagcacgt tggccagttt tcctcaactt 721 gaagtgcaag attctcttat ttccgggacc acggagagtc tgacttaact acatacatct 781 tctgctggtg ttttgttcaa tctggaagaa tgactgtatc agtcaatggg gattttaaca 841 gactgccttg gtactgccga gtcctctcaa aacaaacacc ctcttgcaac cagctttgga 901 gaaagcccag ctcctgtgtg ctcactggga gtggaatccc tgtctccaca tctgctccta 961 gcagtgcatc agccagtaaa acaaacacat ttacaagaaa aatgttttaa agatgccagg 1021 ggtactgaat ctgcaaagca aatgagcagc caaggaccag catctgtccg catttcacta 1081 tcatactacc tcttctttct gtagggatga gaattcctct tttaatcagt caagggagat 1141 gcttcaaagc tggagctatt ttatttctga gatgttgatg tgaactgtac attagtacat 1201 actcagtact ctccttcaat tgctgaaccc cagttgacca ttttaccaag actttagatg 1261 ctttcttgtg ccctcaattt tctttttaaa aatacttcta catgactgct tgacagccca 1321 acagccactc tcaatagaga gctatgtctt acattctttc ctctgctgct caatagtttt 1381 atatatctat gcatacatat atacacacat atgtatataa aattcataat gaatatattt 1441 gcctatattc tccctacaag aatatttttg ctccagaaag acatgttctt ttctcaaatt 1501 cagttaaaat ggtttacttt gttcaagtta gtggtaggaa acattgcccg gaattgaaag 1561 caaatttatt ttattatcct attttctacc attatctatg ttttcatggt gctattaatt 1621 acaagtttag ttctttttgt agatcatatt aaaattgcaa acaaaatcat ctttaatggg 1681 ccagcattct catggggtag agcagaatat tcatttagcc tgaaagctgc agttactata 1741 ggttgctgtc agactatacc catggtgcct ctgggcttga caggtcaaaa tggtccccat 1801 cagcctggag cagccctcca gacctgggtg gaattccagg gttgagagac tcccctgagc 1861 cagaggccac taggtattct tgctcccaga ggctgaagtc accctgggaa tcacagtggt 1921 ctacctgcat tcataattcc aggatctgtg aagagcacat atgtgtcagg gcacaattcc 1981 ctctcataaa aaccacacag cctggaaatt ggccctggcc cttcaagata gccttcttta 2041 gaatatgatt tggctagaaa gattcttaaa tatgtggaat atgattattc ttagctggaa 2101 tattttctct acttcctgtc tgcatgccca aggcttctga agcagccaat gtcgatgcaa 2161 caacatttgt aactttaggt aaactgggat tatgttgtag tttaacattt tgtaactgtg 2221 tgcttatagt ttacaagtga gacccgatat gtcattatgc atacttatat tatcttaagc 2281 atgtgtaatg ctggatgtgt acagtacagt actgaacttg taatttgaat ctagtatggt 2341 gttctgtttt cagctgactt ggacaacctg actggctttg cacaggtgtt ccctgagttg 2401 tttgcaggtt tctgtgtgtg gggtggggta tggggaggag aaccttcatg gtggcccacc 2461 tggcctggtt gtccaagctg tgcctcgaca catcctcatc cccagcatgg gacacctcaa 2521 gatgaataat aattcacaaa atttctgtga aatcaaatcc agttttaaga ggagccactt 2581 atcaaagaga ttttaacagt agtaagaagg caaagaataa acatttgata ttcagcaact 2641 gaaaaaaaaa aa

An exemplary human EOMES amino acid sequence is set forth below (SEQ ID NO: 182; GenBank Accession No: NP_001265111.1, Version 1, incorporated herein by reference):

1 mqlgeqllvs svnlpgahfy plesarggsg gsaghlpsaa pspqkldldk askkfsgsls 61 ceavsgepaa asagapaaml sdtdagdafa saaavakpgp pdgrkgspcg eeelpsaaaa 121 aaaaaaaaaa tarysmdsls seryylqspg pqgselaapc slfpyqaaag aphgpvypap 181 ngarypygsm lppggfpaav cppgraqfgp gagagsgagg ssgggggpgt yqysqgaply 241 gpypgaaaag scgglgglgv pgsgfrahvy lcnrplwlkf hrhqtemiit kqgrrmfpfl 301 sfninglnpt ahynvfvevv ladpnhwrfq ggkwvtcgka dnnmqgnkmy vhpespntgs 361 hwmrqeisfg klkltnnkga nnnntqmivl qslhkyqprl hivevtedgv edlnepsktq 421 tftfsetqfi avtayqntdi tqlkidhnpf akgfrdnyds mytasendrl tpsptdsprs 481 hqivpggryg vqsffpepfv ntlpqaryyn gertvpqtng llspqqseev anppqrwlvt 541 pvqqpgtnkl dissyeseyt sstllpygik slplqtshal gyypdptfpa magwggrgsy 601 qrkmaaglpw tsrtsptvfs edqlskekvk eeigsswiet ppsiksldsn dsgvytsack 661 rrrlspsnss nenspsikce dinaeeyskd tskgmggyya fyttp

An exemplary human EOMES nucleic acid sequence is set forth below (SEQ ID NO: 183; GenBank Accession No: NM_001278182.1, Version 1, incorporated herein by reference):

1 aagtttccaa gtggtcaact tgaccgatgc tttggcaatt gaaaaagggc agaaaggcgc 61 gggctagtgg gtggatgggg acaaagatct aagtcacctt cttccagcgt gtgagcctgg 121 gaggagggtg ggggtcctga ggagcaagag gtacgaggaa ggaaaaggag agggcttctg 181 ggttagtttc cacctcctgc tttccaactc acggcgcttt ccttccggaa aggacgctgg 241 attcagggcg cgccagtacg cgcagtagcg gcccgcgagt cggcaggtgg gtagccccgg 301 cgcgggagga aggggaagtt accttcccct cggaagaggg cgctggctcc cccatcctgc 361 ctttataata aggccaccgg aggagaggaa gcagccagct gccgtctgcg ctttgcaaag 421 catgcagtta ggggagcagc tcttggtgag ctcagtgaac ctgcctggcg cgcacttcta 481 cccgctggag agtgcgcgag gcggcagcgg cgggagcgct ggccacctcc ccagcgcggc 541 cccctctcct cagaagttgg acttagacaa agcgtccaag aagttttccg gcagtctctc 601 ctgcgaggcg gtgagcgggg agcccgcagc cgccagcgca ggggcccccg cggccatgct 661 tagtgacacc gacgccgggg acgcatttgc cagcgctgcg gcagtggcca agccggggcc 721 cccggacggc cgcaagggct ccccctgcgg ggaggaggag ctgccctccg ccgctgcagc 781 cgccgccgcc gccgccgccg cggctgcggc cactgcgcgc tactccatgg acagcctgag 841 ctccgagcgg tactacctcc agtcccccgg tcctcagggg tcggagctgg ctgcgccctg 901 ctcactcttc ccgtaccagg cggcggctgg ggcgccccac ggacctgtgt acccggctcc 961 taacggggcg cgctacccct acggctccat gctgcccccc ggcggcttcc ccgcggctgt 1021 gtgcccaccc gggagggcgc agttcggccc aggagccggt gcgggcagtg gcgcgggcgg 1081 tagcagcggc gggggcggcg gcccgggcac ctatcagtac agccaggggg ctccgctcta 1141 cgggccgtac cctggagccg cagcggcggg atcttgcgga ggactggggg gcctgggggt 1201 tccaggttct ggcttccgtg cccacgtcta cctgtgcaac cggcctctgt ggctcaaatt 1261 ccaccgccac caaactgaga tgatcattac gaaacagggc aggcgcatgt ttcctttctt 1321 gagcttcaac ataaacggac tcaatcccac tgcccactac aatgtgttcg tagaggtggt 1381 gctggcggac cccaaccact ggcgcttcca ggggggcaaa tgggtgacct gtggcaaagc 1441 cgacaataac atgcagggca acaaaatgta tgttcaccca gagtctccta atactggttc 1501 ccactggatg agacaggaga tttcattcgg gaaattaaaa ctcaccaata acaaaggcgc 1561 aaataacaac aacacccaga tgatagtctt acaatcctta cacaaatacc aaccccgact 1621 gcatattgtt gaagttacag aggatggcgt ggaggacttg aatgagccct caaagaccca 1681 gacttttacc ttctcagaaa cgcaattcat tgcagtgact gcctaccaaa acaccgatat 1741 tactcaacta aagattgatc ataacccctt tgcaaaaggc ttcagagaca actatgattc 1801 catgtacacc gcttcagaaa atgacaggtt aactccatct cccacggatt ctcctagatc 1861 ccatcagatt gtccctggag gtcggtacgg cgttcaatcc ttcttcccgg agccctttgt 1921 caacacttta cctcaagccc gctattataa tggcgagaga accgtgccac agaccaacgg 1981 cctcctttca ccccaacaga gcgaagaggt ggccaaccct ccccagcggt ggcttgtcac 2041 gcctgtccag caacctggga ccaacaaact agacatcagt tcctatgaat ctgaatatac 2101 ttctagcaca ttgctcccat atggcattaa atccttgccc cttcagacat cccatgccct 2161 ggggtattac ccagacccaa cctttcctgc aatggcaggg tggggaggtc gaggttctta 2221 ccagaggaag atggcagctg gactaccatg gacctccaga acaagcccca ctgtgttctc 2281 tgaagatcag ctctccaagg agaaagtgaa agaggaaatt ggctcttctt ggatagagac 2341 acccccttcc atcaaatctc tagattccaa tgattcagga gtatacacca gtgcttgtaa 2401 gcgaaggcgg ctgtctccta gcaactccag taatgaaaat tcaccctcca taaagtgtga 2461 ggacattaat gctgaagagt atagtaaaga cacctcaaaa ggcatgggag ggtattatgc 2521 tttttacaca actccctaaa gagttatttt aacctcaaaa attagctaac tttttgcaga 2581 tggacttggt ggtgtttttt gttgtcttct ttgcctaggt tgccaaaaag atgtttgcct 2641 tccaccttga tgcatcctgt tttgtgcaat tctctaaaag aaggtgccaa agctttttga 2701 ttgctgcagg taactgaaac aaacctagca tttttaaaaa ataagattaa tggaagactt 2761 taaggtattt taaaattcga agggtatcca aggttctgta tttatttatt ggggagacac 2821 taacccttca aagaagcagg ctgtgaacat tgggtgccca gtgctatcag atgagttaaa 2881 acctttgatt ctcatttcta tttgtaaatt cttaagcaaa tagaagccga gtgttaaggt 2941 gttttgcttc tgaaagaggg ctgtgccttc cgtttcagaa ggagacattt tgctgttaca 3001 ttctgccagg ggcaaaagat actaggccca ggagtcaaga aaagcttttg tgaaagtgat 3061 agtttcacct gactttgatt ccttaacccc cggcttttgg aacaagccat gtttgcccta 3121 gtccaggatt gcctcacttg agacttgcta ggcctctgct gtgtgctggg gtggccagtg 3181 ggactcagga gagagcaagc taaggagtca ccaaaaaaaa aaaaaaaaaa aagggagaat 3241 ttaaaagtgt acagttgtgt gtttagatac actatagaat aatgtggtat atattgtaca 3301 aatagtctac ataggtgtct gggataatgt aaaactggtg ctttggcttt gtaaagaatt 3361 tgcaaatcac ttaacagctg caggggcaag gggagagttt catcatcccc atgatatttg 3421 ggaatattct gtttacttct tagatagtta agaatgtatt cagctactat gtactaactt 3481 gaaccgtgtt taaggaaaac tcctatttca tcctcttctt gcgccatccc ctctccctaa 3541 cttggtaatg tgaagaaact aaaacctgat accacagctc ctataggcat tttagagatc 3601 ttggattttt atgtacagtc ttagtcattt ttaataaatg tggttcagta agggaacgga 3661 aaaaaaaaaa aaaa

An exemplary human IL2RB amino acid sequence is set forth below (SEQ ID NO: 184; GenBank Accession No: CAG30392.1, Version 1, incorporated herein by reference):

1 maapalswrl pllilllpla tswasaavng tsqftcfyns raniscvwsq dgalqdtscq 61 vhawpdrrrw nqtcellpvs qaswacnlil gapdsqkltt vdivtlrvlc regvrwrvma 121 iqdfkpfenl rlmapislqv vhvethrcni sweisqashy ferhlefear tlspghtwee 181 aplltlkqkq ewicletltp dtqyefqvrv kplqgefttw spwsqplafr tkpaalgkdt 241 ipwlghllvg lsgafgfiil vyllincrnt gpwlkkvlkc ntpdpskffs qlssehggdv 301 qkwlsspfps ssfspgglap eisplevler dkvtqlllqq dkvpepasls snhsltscft 361 nqgyfffhlp daleieacqv yftydpysee dpdegvagap tgsspqplqp lsgeddayct 421 fpsrddlllf spsllggpsp pstapggsga geermppslq ervprdwdpq plgpptpgvp 481 dlvdfqpppe lvlreageev pdagpregvs fpwsrppgqg efralnarlp lntdaylslq 541 elqgqdpthl v

An exemplary human IL2RB nucleic acid sequence is set forth below (SEQ ID NO: 185; GenBank Accession No: NM_000878.3, Version 3, incorporated herein by reference):

1 gcagccagag ctcagcaggg ccctggagag atggccacgg tcccagcacc ggggaggact 61 ggagagcgcg cgctgccacc gccccatgtc tcagccaggg cttccttcct cggctccacc 121 ctgtggatgt aatggcggcc cctgctctgt cctggcgtct gcccctcctc atcctcctcc 181 tgcccctggc tacctcttgg gcatctgcag cggtgaatgg cacttcccag ttcacatgct 241 tctacaactc gagagccaac atctcctgtg tctggagcca agatggggct ctgcaggaca 301 cttcctgcca agtccatgcc tggccggaca gacggcggtg gaaccaaacc tgtgagctgc 361 tccccgtgag tcaagcatcc tgggcctgca acctgatcct cggagcccca gattctcaga 421 aactgaccac agttgacatc gtcaccctga gggtgctgtg ccgtgagggg gtgcgatgga 481 gggtgatggc catccaggac ttcaagccct ttgagaacct tcgcctgatg gcccccatct 541 ccctccaagt tgtccacgtg gagacccaca gatgcaacat aagctgggaa atctcccaag 601 cctcccacta ctttgaaaga cacctggagt tcgaggcccg gacgctgtcc ccaggccaca 661 cctgggagga ggcccccctg ctgactctca agcagaagca ggaatggatc tgcctggaga 721 cgctcacccc agacacccag tatgagtttc aggtgcgggt caagcctctg caaggcgagt 781 tcacgacctg gagcccctgg agccagcccc tggccttcag gacaaagcct gcagcccttg 841 ggaaggacac cattccgtgg ctcggccacc tcctcgtggg cctcagcggg gcttttggct 901 tcatcatctt agtgtacttg ctgatcaact gcaggaacac cgggccatgg ctgaagaagg 961 tcctgaagtg taacacccca gacccctcga agttcttttc ccagctgagc tcagagcatg 1021 gaggagacgt ccagaagtgg ctctcttcgc ccttcccctc atcgtccttc agccctggcg 1081 gcctggcacc tgagatctcg ccactagaag tgctggagag ggacaaggtg acgcagctgc 1141 tcctgcagca ggacaaggtg cctgagcccg catccttaag cagcaaccac tcgctgacca 1201 gctgcttcac caaccagggt tacttcttct tccacctccc ggatgccttg gagatagagg 1261 cctgccaggt gtactttact tacgacccct actcagagga agaccctgat gagggtgtgg 1321 ccggggcacc cacagggtct tccccccaac ccctgcagcc tctgtcaggg gaggacgacg 1381 cctactgcac cttcccctcc agggatgacc tgctgctctt ctcccccagt ctcctcggtg 1441 gccccagccc cccaagcact gcccctgggg gcagtggggc cggtgaagag aggatgcccc 1501 cttctttgca agaaagagtc cccagagact gggaccccca gcccctgggg cctcccaccc 1561 caggagtccc agacctggtg gattttcagc caccccctga gctggtgctg cgagaggctg 1621 gggaggaggt ccctgacgct ggccccaggg agggagtcag tttcccctgg tccaggcctc 1681 ctgggcaggg ggagttcagg gcccttaatg ctcgcctgcc cctgaacact gatgcctact 1741 tgtccctcca agaactccag ggtcaggacc caactcactt ggtgtagaca gatggccagg 1801 gtgggaggca ggcagctgcc tgctctgcgc cgagcctcag aaggaccctg ttgagggtcc 1861 tcagtccact gctgaggaca ctcagtgtcc agttgcagct ggacttctcc acccggatgg 1921 cccccaccca gtcctgcaca cttggtccat ccatttccaa acctccactg ctgctcccgg 1981 gtcctgctgc ccgagccagg aactgtgtgt gttgcagggg ggcagtaact ccccaactcc 2041 ctcgttaatc acaggatccc acgaatttag gctcagaagc atcgctcctc tccagccctg 2101 cagctattca ccaatatcag tcctcgcggc tctccagggc tccctgccct gacctcttcc 2161 ctgggttttc tgccccagcc tcctccttcc ctcccctccc cgtccacagg gcagcctgag 2221 cgtgctttcc aaaacccaaa tatggccacg ctccccctcg gttcaaaacc ttgcacaggt 2281 cccactgccc tcagccccac ttctcagcct ggtacttgta cctccggtgt cgtgtgggga 2341 catccccttc tgcaatcctc cctaccgtcc tcctgagcca ctcagagctc cctcacaccc 2401 cctctgttgc acatgctatt ccctggggct gctgtgcgct ccccctcatc taggtgacaa 2461 acttccctga ctcttcaagt gccggttttg cttctcctgg agggaagcac tgcctccctt 2521 aatctgccag aaacttctag cgtcagtgct ggagggagaa gctgtcaggg acccagggcg 2581 cctggagaaa gaggccctgt tactattcct ttgggatctc tgaggcctca gagtgcttgg 2641 ctgctgtatc tttaatgctg gggcccaagt aagggcacag atccccccac aaagtggatg 2701 cctgctgcat cttcccacag tggcttcaca gacccacaag agaagctgat ggggagtaaa 2761 ccctggagtc cgaggcccag gcagcagccc cgcctagtgg tgggccctga tgctgccagg 2821 cctgggacct cccactgccc cctccactgg aggggtctcc tctgcagctc agggactggc 2881 acactggcct ccagaagggc agctccacag ggcagggcct cattattttt cactgcccca 2941 gacacagtgc ccaacacccc gtcgtatacc ctggatgaac gaattaatta cctggcacca 3001 cctcgtctgg gctccctgcg cctgacattc acacagagag gcagagtccc gtgcccatta 3061 ggtctggcat gccccctcct gcaaggggct caacccccta ccccgacccc tccacgtatc 3121 tttcctaggc agatcacgtt gcaatggctc aaacaacatt ccaccccagc aggacagtga 3181 ccccagtccc agctaactct gacctgggag ccctcaggca cctgcactta caggccttgc 3241 tcacagctga ttgggcacct gaccacacgc ccccacaggc tctgaccagc agcctatgag 3301 ggggtttggc accaagctct gtccaatcag gtaggctggg cctgaactag ccaatcagat 3361 caactctgtc ttgggcgttt gaactcaggg agggaggccc ttgggagcag gtgcttgtgg 3421 acaaggctcc acaagcgttg agccttggaa aggtagacaa gcgttgagcc actaagcaga 3481 ggaccttggg ttcccaatac aaaaatacct actgctgaga gggctgctga ccatttggtc 3541 aggattcctg ttgcctttat atccaaaata aactcccctt tcttgaggtt gtctgagtct 3601 tgggtctatg ccttgaaaaa agctgaatta ttggacagtc tcacctcctg ccatagggtc 3661 ctgaatgttt cagaccacaa ggggctccac acctttgctg tgtgttctgg ggcaacctac 3721 taatcctctc tgcaagtcgg tctccttatc cccccaaatg gaaattgtat ttgccttctc 3781 cactttggga ggctcccact tcttgggagg gttacatttt ttaagtctta atcatttgtg 3841 acatatgtat ctatacatcc gtatctttta atgatccgtg tgtaccatct ttgtgattat 3901 ttccttaata ttttttcttt aagtcagttc attttcgttg aaatacattt atttaaagaa 3961 aaatctttgt tactctgtaa atgaaaaaac ccattttcgc tataaataaa aggtaactgt 4021 acaaaataag tacaatgcaa caaaaaaaaa

An exemplary human FASLG amino acid sequence is set forth below (SEQ ID NO: 186; GenBank Accession No: AAH17502.1, Version 1, incorporated herein by reference):

1 mqqpfnypyp qiywvdssas spwappgtvl pcptsvprrp gqrrpppppp ppplpppppp 61 pplpplplpp lkkrgnhstg lcllvmffmv lvalvglglg mfqlfhlqke laelrestsq 121 mhtasslekq ighpspppek kelrkvahlt gksnsrsmpl ewedtygivl lsgvkykkgg 181 lvinetglyf vyskvyfrgq scnnlplshk vymrnskypq dlvmmegkmm sycttgqmwa 241 rssylgavfn ltsadhlyvn vselslvnfe esqtffglyk l

An exemplary human FASLG nucleic acid sequence is set forth below (SEQ ID NO: 187; GenBank Accession No: NM_000639.2, Version 2, incorporated herein by reference):

1 agaatcagag agagagagat agagaaagag aaagacagag gtgtttccct tagctatgga 61 aactctataa gagagatcca gcttgcctcc tcttgagcag tcagcaacag ggtcccgtcc 121 ttgacacctc agcctctaca ggactgagaa gaagtaaaac cgtttgctgg ggctggcctg 181 actcaccagc tgccatgcag cagcccttca attacccata tccccagatc tactgggtgg 241 acagcagtgc cagctctccc tgggcccctc caggcacagt tcttccctgt ccaacctctg 301 tgcccagaag gcctggtcaa aggaggccac caccaccacc gccaccgcca ccactaccac 361 ctccgccgcc gccgccacca ctgcctccac taccgctgcc acccctgaag aagagaggga 421 accacagcac aggcctgtgt ctccttgtga tgtttttcat ggttctggtt gccttggtag 481 gattgggcct ggggatgttt cagctcttcc acctacagaa ggagctggca gaactccgag 541 agtctaccag ccagatgcac acagcatcat ctttggagaa gcaaataggc caccccagtc 601 caccccctga aaaaaaggag ctgaggaaag tggcccattt aacaggcaag tccaactcaa 661 ggtccatgcc tctggaatgg gaagacacct atggaattgt cctgctttct ggagtgaagt 721 ataagaaggg tggccttgtg atcaatgaaa ctgggctgta ctttgtatat tccaaagtat 781 acttccgggg tcaatcttgc aacaacctgc ccctgagcca caaggtctac atgaggaact 841 ctaagtatcc ccaggatctg gtgatgatgg aggggaagat gatgagctac tgcactactg 901 ggcagatgtg ggcccgcagc agctacctgg gggcagtgtt caatcttacc agtgctgatc 961 atttatatgt caacgtatct gagctctctc tggtcaattt tgaggaatct cagacgtttt 1021 tcggcttata taagctctaa gagaagcact ttgggattct ttccattatg attctttgtt 1081 acaggcaccg agaatgttgt attcagtgag ggtcttctta catgcatttg aggtcaagta 1141 agaagacatg aaccaagtgg accttgagac cacagggttc aaaatgtctg tagctcctca 1201 actcacctaa tgtttatgag ccagacaaat ggaggaatat gacggaagaa catagaactc 1261 tgggctgcca tgtgaagagg gagaagcatg aaaaagcagc taccaggtgt tctacactca 1321 tcttagtgcc tgagagtatt taggcagatt gaaaaggaca ccttttaact cacctctcaa 1381 ggtgggcctt gctacctcaa gggggactgt ctttcagata catggttgtg acctgaggat 1441 ttaagggatg gaaaaggaag actagaggct tgcataataa gctaaagagg ctgaaagagg 1501 ccaatgcccc actggcagca tcttcacttc taaatgcata tcctgagcca tcggtgaaac 1561 taacagataa gcaagagaga tgttttgggg actcatttca ttcctaacac agcatgtgta 1621 tttccagtgc aattgtaggg gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtatgactaa 1681 agagagaatg tagatattgt gaagtacata ttaggaaaat atgggttgca tttggtcaag 1741 attttgaatg cttcctgaca atcaactcta atagtgctta aaaatcattg attgtcagct 1801 actaatgatg ttttcctata atataataaa tatttatgta gatgtgcatt tttgtgaaat 1861 gaaaacatgt aataaaaagt atatgttagg atacaaaaaa aaaaaaa

An exemplary human SLAMF6 amino acid sequence is set forth below (SEQ ID NO: 188; GenBank Accession No: AAI14496.1, Version 1, incorporated herein by reference):

1 mlwlfqsllf vfcfgpgnvv sqssltplmv ngilgesvtl plefpagekv nfitwlfnet 61 slafivphet kspeihvtnp kqgkrinftq syslqlsnlk medtgsyraq istktsakls 121 sytlrilrql rniqvtnhsq lfqnmtcelh ltcsvedadd nvsfrwealg ntlssqpnlt 181 vswdprisse qdytciaena vsnlsfsysa qklcedvkiq ytdtkmilfm vsgicivfgf 241 iillllvlrk rrdslslstq rtqgpaesar nleyvsyspt nntvyasvth snreteiwtp 301 rendtitiys tinhskeskp tfsrataldn vv

An exemplary human SLAMF6 nucleic acid sequence is set forth below (SEQ ID NO: 189; GenBank Accession No: NM_001184714.1, Version 1, incorporated herein by reference):

1 agtttatgac agaagggcaa aaacattgac tgcctcaagg tctcaagcac cagtcttcac 61 cgcggaaagc atgttgtggc tgttccaatc gctcctgttt gtcttctgct ttggcccagg 121 gaatgtagtt tcacaaagca gcttaacccc attgatggtg aacgggattc tgggggagtc 181 agtaactctt cccctggagt ttcctgcagg agagaaggtc aacttcatca cttggctttt 241 caatgaaaca tctcttgcct tcatagtacc ccatgaaacc aaaagtccag aaatccacgt 301 gactaatccg aaacagggaa agcgactgaa cttcacccag tcctactccc tgcaactcag 361 caacctgaag atggaagaca caggctctta cagagcccag atatccacaa agacctctgc 421 aaagctgtcc agttacactc tgaggatatt aagacaactg aggaacatac aagttaccaa 481 tcacagtcag ctatttcaga atatgacctg tgagctccat ctgacttgct ctgtggagga 541 tgcagatgac aatgtctcat tcagatggga ggccttggga aacacacttt caagtcagcc 601 aaacctcact gtctcctggg accccaggat ttccagtgaa caggactaca cctgcatagc 661 agagaatgct gtcagtaatt tatccttctc tgtctctgcc cagaagcttt gcgaagatgt 721 taaaattcaa tatacagata ccaaaatgat tctgtttatg gtttctggga tatgcatagt 781 cttcggtttc atcatactgc tgttacttgt tttgaggaaa agaagagatt ccctatcttt 841 gtctactcag cgaacacagg gccccgcaga gtccgcaagg aacctagagt atgtttcagt 901 gtctccaacg aacaacactg tgtatgcttc agtcactcat tcaaacaggg aaacagaaat 961 ctggacacct agagaaaatg atactatcac aatttactcc acaattaatc attccaaaga 1021 gagtaaaccc actttttcca gggcaactgc ccttgacaat gtcgtgtaag ttgctgaaag 1081 gcctcagagg aattcgggaa tgacacgtct tctgatccca tgagacagaa caaagaacag 1141 gaagcttggt tcctgttgtt cctggcaaca gaatttgaat atctaggata ggatgatcac 1201 ctccagtcct tcggacttaa acctgcctac ctgagtcaaa cacctaagga taacatcatt 1261 tccagcatgt ggttcaaata atattttcca atccacttca ggccaaaaca tgctaaagat 1321 aacacaccag cacattgact ctctctttga taactaagca aatggaatta tggttgacag 1381 agagtttatg atccagaaga caaccacttc tctcctttta gaaagcagca ggattgactt 1441 attgagaaat aatgcagtgt gttggttaca tgtgtagtct ctggagttgg atgggcccat 1501 cctgatacaa gttgagcatc ccttgtctga aatgcttggg attagaaatg tttcagattt 1561 caattttttt tcagattttg gaatatttgc attatattta gcggttgagt atccaaatcc 1621 aaaaatccaa aattcaaaat gctccaataa gcatttccct tgagtttcat tgatgtcgat 1681 gcagtgctca aaatctcaga ttttggagca ttttggatat tggatttttg gatttgggat 1741 gctcaacttg tacaatgttt attagacaca tctcctggga catactgcct aaccttttgg 1801 agccttagtc tcccagactg aaaaaggaag aggatggtat tacatcagct ccattgtttg 1861 agccaagaat ctaagtcatc cctgactcca gtgtctttgt caccaggccc tttggactct 1921 acctcagaaa tatttcttgg accttccact tctcctccaa ctccttgacc accatcctgt 1981 atccaaccat caccacctct aacctgaatc ctaccttaag atcagaacag ttgtcctcac 2041 ttttgttctt gtccctctcc aacccactct ccacaagatg gccagagtaa tgtttttaat 2101 ataaattgga tccttcagtt tcctgcttaa aaccctgcag gtttcccaat gcactcagaa 2161 agaaatccag tttccatggc cctggatggt ctggcccacc tccagcctca gctagcatta 2221 cccttctgac actctctatg tagcctccct gatcttcttt cagctcctct attaaaggaa 2281 aagttcttta tgttaattat ttacatcttc ctgcaggccc ttcctctgcc tgctggggtc 2341 ctcctattct ttaggtttaa ttttaaatat gtcacctcct aagagaaacc ttcccagacc 2401 actctttcta aaatgaatct tctaggctgg gcatggtggc tcacacctgt aatccctgta 2461 ctttgggagg ccaagggggg agatcacttg aggtcaggag ttcaagacca gcctggccaa 2521 cttggtgaaa ccccgtcttt actaaaaata caaaaaaatt agccaggcgt ggtggtgcac 2581 ccctaaaatc ccagctactt gagagactga ggcaggagaa tcgcttgaac ccaggaggtg 2641 gaggttccag tgagccaaaa tcatgccaat gtattccagt ctgggtgaca gagtgagact 2701 ctgtctcaaa aaataaataa ataaaataaa atgaaataga tcttataaaa aaaa

An exemplary human GAPDH amino acid sequence is set forth below (SEQ ID NO: 190; GenBank Accession No: NP_001276675.1, Version 1, incorporated herein by reference):

1 mgkvkvgvng fgrigrlvtr aafnsgkvdi vaindpfidl nymvymfqyd sthgkfhgtv 61 kaengklvin gnpitifqer dpskikwgda gaeyvvestg vfttmekaga hlqggakrvi 121 isapsadapm fvmgvnheky dnslkiisna scttnclapl akvihdnfgi veglmttvha 181 itatqktvdg psgklwrdgr galqniipas tgaakavgkv ipelngkltg mafrvptanv 241 svvdltcrle kpakyddikk vvkqasegpl kgilgytehq vvssdfnsdt hsstfdagag 301 ialndhfvkl iswydnefgy snrvvdlmah maske

An exemplary human GAPDH nucleic acid sequence is set forth below (SEQ ID NO: 191; GenBank Accession No: NM_002046.5, Version 5, incorporated herein by reference):

1 gcctcaagac cttgggctgg gactggctga gcctggcggg aggcggggtc cgagtcaccg 61 cctgccgccg cgcccccggt ttctataaat tgagcccgca gcctcccgct tcgctctctg 121 ctcctcctgt tcgacagtca gccgcatctt cttttgcgtc gccagccgag ccacatcgct 181 cagacaccat ggggaaggtg aaggtcggag tcaacggatt tggtcgtatt gggcgcctgg 241 tcaccagggc tgcttttaac tctggtaaag tggatattgt tgccatcaat gaccccttca 301 ttgacctcaa ctacatggtt tacatgttcc aatatgattc cacccatggc aaattccatg 361 gcaccgtcaa ggctgagaac gggaagcttg tcatcaatgg aaatcccatc accatcttcc 421 aggagcgaga tccctccaaa atcaagtggg gcgatgctgg cgctgagtac gtcgtggagt 481 ccactggcgt cttcaccacc atggagaagg ctggggctca tttgcagggg ggagccaaaa 541 gggtcatcat ctctgccccc tctgctgatg cccccatgtt cgtcatgggt gtgaaccatg 601 agaagtatga caacagcctc aagatcatca gcaatgcctc ctgcaccacc aactgcttag 661 cacccctggc caaggtcatc catgacaact ttggtatcgt ggaaggactc atgaccacag 721 tccatgccat cactgccacc cagaagactg tggatggccc ctccgggaaa ctgtggcgtg 781 atggccgcgg ggctctccag aacatcatcc ctgcctctac tggcgctgcc aaggctgtgg 841 gcaaggtcat ccctgagctg aacgggaagc tcactggcat ggccttccgt gtccccactg 901 ccaacgtgtc agtggtggac ctgacctgcc gtctagaaaa acctgccaaa tatgatgaca 961 tcaagaaggt ggtgaagcag gcgtcggagg gccccctcaa gggcatcctg ggctacactg 1021 agcaccaggt ggtctcctct gacttcaaca gcgacaccca ctcctccacc tttgacgctg 1081 gggctggcat tgccctcaac gaccactttg tcaagctcat ttcctggtat gacaacgaat 1141 ttggctacag caacagggtg gtggacctca tggcccacat ggcctccaag gagtaagacc 1201 cctggaccac cagccccagc aagagcacaa gaggaagaga gagaccctca ctgctgggga 1261 gtccctgcca cactcagtcc cccaccacac tgaatctccc ctcctcacag ttgccatgta 1321 gaccccttga agaggggagg ggcctaggga gccgcacctt gtcatgtacc atcaataaag 1381 taccctgtgc tcaaccagtt aaaaaaaaaa aaaaaaaaaa a

An exemplary human HPRT1 amino acid sequence is set forth below (SEQ ID NO: 192; GenBank Accession No: AAH00578.1, Version 1, incorporated herein by reference):

1 matrspgvvi sddepgydld lfcipnhyae dlervfiphg limdrterla rdvmkemggh 61 hivalcvlkg gykffadlld yikalnrnsd rsipmtvdfi rlksycndqs tgdikviggd 121 dlstltgknv livediidtg ktmqtllslv rqynpkmvkv asllvkrtpr svgykpdfvg 181 feipdkfvvg yaldyneyfr dlnhvcvise tgkakyka

An exemplary human HPRT1 nucleic acid sequence is set forth below (SEQ ID NO: 193; GenBank Accession No: NM_000194.2, Version 2, incorporated herein by reference):

1 ggcggggcct gcttctcctc agcttcaggc ggctgcgacg agccctcagg cgaacctctc 61 ggctttcccg cgcggcgccg cctcttgctg cgcctccgcc tcctcctctg ctccgccacc 121 ggcttcctcc tcctgagcag tcagcccgcg cgccggccgg ctccgttatg gcgacccgca 181 gccctggcgt cgtgattagt gatgatgaac caggttatga ccttgattta ttttgcatac 241 ctaatcatta tgctgaggat ttggaaaggg tgtttattcc tcatggacta attatggaca 301 ggactgaacg tcttgctcga gatgtgatga aggagatggg aggccatcac attgtagccc 361 tctgtgtgct caaggggggc tataaattct ttgctgacct gctggattac atcaaagcac 421 tgaatagaaa tagtgataga tccattccta tgactgtaga ttttatcaga ctgaagagct 481 attgtaatga ccagtcaaca ggggacataa aagtaattgg tggagatgat ctctcaactt 541 taactggaaa gaatgtcttg attgtggaag atataattga cactggcaaa acaatgcaga 601 ctttgctttc cttggtcagg cagtataatc caaagatggt caaggtcgca agcttgctgg 661 tgaaaaggac cccacgaagt gttggatata agccagactt tgttggattt gaaattccag 721 acaagtttgt tgtaggatat gcccttgact ataatgaata cttcagggat ttgaatcatg 781 tttgtgtcat tagtgaaact ggaaaagcaa aatacaaagc ctaagatgag agttcaagtt 841 gagtttggaa acatctggag tcctattgac atcgccagta aaattatcaa tgttctagtt 901 ctgtggccat ctgcttagta gagctttttg catgtatctt ctaagaattt tatctgtttt 961 gtactttaga aatgtcagtt gctgcattcc taaactgttt atttgcacta tgagcctata 1021 gactatcagt tccctttggg cggattgttg tttaacttgt aaatgaaaaa attctcttaa 1081 accacagcac tattgagtga aacattgaac tcatatctgt aagaaataaa gagaagatat 1141 attagttttt taattggtat tttaattttt atatatgcag gaaagaatag aagtgattga 1201 atattgttaa ttataccacc gtgtgttaga aaagtaagaa gcagtcaatt ttcacatcaa 1261 agacagcatc taagaagttt tgttctgtcc tggaattatt ttagtagtgt ttcagtaatg 1321 ttgactgtat tttccaactt gttcaaatta ttaccagtga atctttgtca gcagttccct 1381 tttaaatgca aatcaataaa ttcccaaaaa tttaaaaaaa aaaaaaaaaa aaaaa

An exemplary human PSK1 amino acid sequence is set forth below (SEQ ID NO: 194; GenBank Accession No: NP_079418.1, Version 1, incorporated herein by reference):

1 mpstnragsl kdpeiaelff kedpeklftd lreighgsfg avyfardvrt nevvaikkms 61 ysgkqstekw qdiikevkfl qrikhpnsie ykgcylreht awlvmeyclg sasdllevhk 121 kplqeveiaa ithgalqgla ylhshtmihr dikagnillt epgqvkladf gsasmaspan 181 sfvgtpywma pevilamdeg qydgkvdvws lgitcielae rkpplfnmna msalyhiaqn 241 esptlqsnew sdyfrnfvds clqkipqdrp tseellkhif vlrerpetvl idliqrtkda 301 vreldnlqyr kmkkllfqea hngpaveaqe eeeeqdhgvg rtgtvnsvgs nqsipsmsis 361 assqsssvns lpdvsddkse ldmmegdhtv msnssvihlk peeenyreeg dprtrasdpq 421 sppqvsrhks hyrnrehfat irtaslvtrq mqeheqdsel reqmsgykrm rrqhqkqlmt 481 lenklkaemd ehrlrldkdl etqrnnfaae meklikkhqa amekeakvms neekkfqqhi 541 qaqqkkelns flesqkreyk lrkeqlkesk elqikkqfqd tckiqtrqyk alrnhllett 601 pksehkavlk rlkeeqtrkl ailaeqydhs inemlstqal rldeaqeaec qvlkmqlqqe 661 lellnayqsk ikmqaeaqhd relreleqrv slrralleqk ieeemlalqn erterirsll 721 erqareieaf dsesmrlgfs nmvlsnlspe afshsypgas gwshnptggp gphwghpmgg 781 ppqawghpmq ggpqpwghps gpmqgvprgs smgvrnspqa lrrtasggrt eqgmsrstsv 841 tsqisngshm syt

An exemplary human PSK1 nucleic acid sequence is set forth below (SEQ ID NO: 195; GenBank Accession No: NM_025142.1, Version 1, incorporated herein by reference):

1 cccctcctcc tcctcactcc tcaccctcca gggtagcggc taccggagcg ctgcaggggg 61 ctgcgcctgc ctgctccgcc ccagacctgt cggcgaaagg tagtttatgc caacgtgact 121 tcattcatac agatgaacca aggatcggga tagcagtata aaattagaat caagacagct 181 gactgctcag caggatgcca tcaactaaca gagcaggcag cctgaaggac cctgaaattg 241 cagagctctt cttcaaagaa gatccagaga agctcttcac agatctcaga gaaattggcc 301 atggaagctt tggagcagtg tattttgcac gagatgtgcg taccaatgaa gtggtggcca 361 tcaagaaaat gtcttatagt ggaaagcagt ctactgagaa atggcaggat attattaagg 421 aagtcaagtt tctacaaaga ataaaacatc ccaacagtat agaatacaaa ggctgttatt 481 tacgtgaaca cacagcatgg cttgtaatgg aatattgttt aggatctgct tcggatttac 541 tagaagttca caaaaagcca ttacaagaag tggaaatagc agcaattaca catggtgctc 601 ttcagggatt agcctactta cattctcata ctatgattca tagagatatc aaagcaggaa 661 atatccttct gacagaacca ggccaggtga aacttgctga ctttggctct gcttccatgg 721 catcacctgc caattccttt gtgggaacgc cgtattggat ggccccagaa gtaattttag 781 ccatggatga aggacaatat gatggcaaag tagatgtgtg gtctcttgga ataacatgta 841 ttgaactagc ggaaaggaag cctcctttat ttaatatgaa tgcaatgagt gccttatatc 901 acatagccca aaatgaatcc cctacactac agtctaatga atggtctgat tattttcgca 961 actttgtaga ttcttgcctc cagaaaatcc ctcaagatcg acctacatca gaggaacttt 1021 taaagcacat atttgttctt cgggagcgcc ctgaaaccgt gttaatagat ctcattcaga 1081 ggacaaagga tgcagtaaga gagctggaca atctgcagta tcgaaagatg aagaaactcc 1141 ttttccagga ggcacataat ggaccagcag tagaagcaca ggaagaagaa gaggaacaag 1201 atcatggtgt tggccggaca ggaacagtta atagtgttgg aagtaatcaa tccattccca 1261 gcatgtccat cagtgccagc agccaaagca gtagtgttaa cagtcttcca gatgtctcag 1321 atgacaagag tgagctagac atgatggagg gagaccacac agtgatgtct aacagttctg 1381 ttatccattt aaaaccagag gaagaaaatt acagagaaga gggagatcct agaacaagag 1441 catcagatcc acaatctcca ccccaagtat ctcgtcacaa atcacactat cgtaatcgag 1501 aacactttgc tactatacgg acagcatcac tggttacgag gcaaatgcaa gaacatgagc 1561 aggactctga gcttagagaa caaatgtctg gctataagcg aatgaggcga caacatcaaa 1621 agcaactgat gactctggaa aacaagctaa aggctgagat ggatgaacat cgcctcagat 1681 tagacaaaga tcttgaaact cagcgtaaca attttgctgc agaaatggag aaacttatca 1741 agaaacacca ggctgccatg gagaaagagg ctaaagtgat gtccaatgaa gagaaaaaat 1801 ttcagcaaca tattcaggcc caacagaaga aagaactgaa tagttttctc gagtcccaga 1861 aaagagagta taaacttcga aaagagcagc ttaaagagtc taaagaactc caaataaaaa 1921 agcagtttca ggatacctgc aaaatccaaa ccagacagta caaagcatta agaaatcacc 1981 tgctggagac tacaccaaag agtgagcaca aagctgttct gaaacggctc aaggaggaac 2041 agacccggaa attagctatc ttggctgagc agtatgatca cagcattaat gaaatgctct 2101 ccacacaagc cctgcgtttg gatgaagcac aggaagcaga gtgccaggtt ttgaagatgc 2161 agctgcagca ggaactggag ctgttgaatg cgtatcagag caaaatcaag atgcaagctg 2221 aggcacaaca tgatcgagag cttcgcgagc ttgaacagag ggtctccctc cggagggcac 2281 tcttagaaca aaagattgaa gaagagatgt tggctttgca gaatgagcgc acagaacgaa 2341 tacgaagcct gttggaacgt caagccagag agattgaagc ttttgactct gaaagcatga 2401 gactaggttt tagtaatatg gtcctttcta atctctcccc tgaggcattc agccacagct 2461 acccgggagc ttctggttgg tcacacaacc ctactggggg tccaggacct cactggggtc 2521 atcccatggg tggcccacca caagcttggg gccatccaat gcaaggtgga ccccagccat 2581 ggggtcaccc ttcagggcca atgcaagggg tacctcgagg tagcagtatg ggagtccgca 2641 atagccccca ggctctgagg cggacagctt ctgggggacg gacggagcag ggcatgagca 2701 gaagcacgag tgtcacttca caaatatcca atgggtcaca catgtcttat acataactta 2761 ataattgaga gtggcaattc cgctggagct gtctgccaaa agaaactgcc tacagacatc 2821 atcacagcag cctcctcact tgggtactac agtgtggaag ctgagtgcat atggtatatt 2881 ttattcattt ttgtaaagcg ttctgttttg tgtttactaa ttgggatgtc atagtacttg 2941 gctgccgggt ttgtttgttt ttggggaaat tttgaaaagt ggagttgata ttaaaaataa 3001 atgtgtatgt gtgtacatat atatacacac acatacacat atattatgca tgtggtgaaa 3061 agaattggct agatagggga tttttctgaa cactgcaaaa atagaacgta gcaaaatggc 3121 ttcagttatc acttttgggt gtctgtatcc taagaagttt ctgaaaagat ctaaagcctt 3181 tttatcccat atcccaaatt cttatgagcc actcacagca ggcagcatat gttgaaataa 3241 gttattactg gtacacacct gcattgcctc accagtgtat ttatttgtta ttaaattgat 3301 ctgacttctc agcctcattt ggactaaaaa aagaaagcag aaatccatga acacattgct 3361 tctcggcctt ttggctaaga tcaagtgtag aaatccatga acactaaagg acttcattga 3421 ttttttcaga gagtagaaaa caacttagtt tttctttttt cctgaatgcg tcataggctt 3481 gtgagtgatt tttgtccatt caattgtgcc ttctttgtat tatgataaga tgggggtact 3541 taaggagatc acaagttgtg tgaggattgc attaacaaac ctatgagcct tcaatgggga 3601 agaccagaag ggtgagaggg gccctgaaag ttcatatggt gggtatgtcc cgcagcagag 3661 tgaggagatg aagcttacgt gtcctgacgt tttgttgctt atactgtgat atctcatcct 3721 agctaagctc tataatgccc aagaccccaa acagtacttt tactttgttt gtacaaaaac 3781 aaagacatat agccaataca aatcaaatgc cggaggtgtt tgatgccata tttgcaaatt 3841 gccatctatt gaaattctcg tcacactaca tagacataat tgttatctcc ttttggctta 3901 tgtgattttc tgtttacaag tagaatagcc aattatttaa atgtttagtt gccacagtga 3961 accaggagtc actgagccaa tgactttacc agctgctgac taatcttcat caccactgta 4021 gattttgctg catgtgcagg tcctctattt ttaattgctg ttttcgttgc tgcagtactt 4081 tacaaacttc tagttcgttg agacttagtg accatttggc atcaagttaa catcacacaa 4141 taggaaacac cacttccaca agtctcaagc ctcagtgcta aagtactact gaaaaggaac 4201 taggaagttt ggccaattaa aaaaaaaaag taaaataagt tatagtggtc agggaatctc 4261 ttgacgaaag ctaactctta tttttcaggg ggcacatgtt ttgttttgtt atgttttgtt 4321 gtacaatgaa ggatgaaccc aatgctaaaa agtcagttat tttcttggtt ttccatttct 4381 tgtatataaa ttgtgttgga ggtgggtagg aagctgtgag tatgacttga agaaaaatat 4441 ccttttcagt gacaaatcag agtttcttac aagttattgt cctgctccct tccaagttgt 4501 cttgaagaat ccttgctgct aactctggat cctgcttttc ctatagtcag agggctccaa 4561 ggtagaactc tctaagtccc tctcaatggc actctttgcc tagaccaaac taatgaccaa 4621 acagtaatca atctatcact gttgaagtcc tggttttctc aaccaaattt taagtctttc 4681 ccaggtatgt cagtcgagtt gccatgaatc ctcacctgta ggagtttctg ggattcattt 4741 taaggaaact ggaagaaaat taatgtttta atgtaaatgt ttttaaaacc aagatcacca 4801 tagagttcac acaaaatttt aggcagtgtt tcaagaagca ctcttatgtg ttgttctttc 4861 agcccatgct ccaggtcacc ggtttttagg taaacatgac atgacatgta cttgtaatat 4921 cagtgaaagg ggcttttagt cgtctcagta tcttttttgc attcaggtat tatagcgttt 4981 ccaacaaatt gagaaattac ttatttggtg taaaatgacg agagagcttt agaatttaat 5041 aaaatgtcaa aaatacaatt tgataccctt aaaaattatt catagatctg gctgctctgt 5101 actactggat gggtggaata gggaagcaga tcacttttgc atacaaaaac tctttcaaac 5161 ccaaaatatt attggtggta cattttaaag tccaattgtg gacttaaatt agtcaaattg 5221 agagttactg agtccattca gatctccagt agggttttgt atctaatgta tttggccacc 5281 agttttacat gtaggtcatg actatacctg gattttatca ttaagttaac tttaaagtat 5341 atacagtttg caaaaaatga ttcaaattaa ttggtttgta tatgtttgtg agatctagct 5401 tctgaggaat ctcatacata gtaggaacca tcatagagta aagcttgtag cagaaaaatt 5461 ggaagggttt tgagatatcc tagagaaaga gcaagcactt tctgaatcag tggggaaata 5521 tcaatatttg atcaaattaa cactacctcc ttcccagtgt tggtgttcac tcactatatg 5581 tctttaagaa aattaaaact atggaaaatt tgtctagcat atcagaagtt gtaaatgcta 5641 tatctggtat ccagaggctg gctgtaaaaa gttccttggg gtcactctat ctcacatttt 5701 ttttggttag cattttaaaa atgcaaagcc acatactttg aaatatatta ttccaaattg 5761 agctcccttc cctttgcaca tattttttcc tccccttatt gaagtcagct ctaaccccaa 5821 attctagtat ccaaaagtat ttttatttgt ataatgctat ctgaaaaatg tgtttatatt 5881 atattttcag agctgcaatt cttattcgcc atttcaatac ctagagatag agagtcttgt 5941 atttgaagcc acacacactg gtgtaatatg cttagtactc taggtcaagg atttgttggt 6001 aaatggaaca ttttagcata gtcatgattt ttggttgcct agacatcagg taaacattca 6061 gtacactaaa gaaactatcc tggacactcc ctcctgcttc caccaatttt tttctcaccc 6121 ccttttcaaa aattgaaaac tctatgagtg tctttttgag accataaagc agactttagt 6181 aactttctat ttctgtaagt actaaatgtc tggcatttta aacttttgta gaatacatta 6241 tgttggacac tggaataata ctatttattt tcacctgtga aaaatgactt cattgtactt 6301 gaaacacctc ctttgcattt ctccatttgt gccattcact agtggaaata aattgtatta 6361 taccatgatc tactggcttt ttaaaactgt attaaatatg cacatttttg gtatagctat 6421 tatcatttgt atgtatatat tgtatataca tatgagtgtc tgtatgtgtg tatagatgga 6481 tggatgtaac tcatactgta catttccatc agggcactta aaagttctgt tatttttgtt 6541 tggttttgtt atttcagtcc tcagttaagg caagaatgca tgtgtttctt aagaatgagt 6601 actctgcgtt gatgtttatg agaaggtggt cattagatgc agtcttttcc tttttaatcc 6661 cctcttagca cttctgtgag tggagaggac attaagtaaa atttggaatc ataagttgca 6721 atgcagtaaa atggtgctgg ggaaggagcc agttagtgtt tctgtgagtt tgtgttgtga 6781 tgcaataaga gataagtaat gcagagagaa atgaaccatg gaaagtaaga acactgatgg 6841 tgattcctct gcaaagatga taagaaaaag aaccaataaa tcacacaatc tttatgtgct 6901 ttctatatgt atttcttagt agtgatacca ttgatcctct tacttttttt actccattaa 6961 tactaataat tatatacttt gctgaggatc aaaacagcca agaaaggaat tactgctaaa 7021 gcatctaaga ttctcctgaa ctgtaaaatc aacaggaaat ggccactggg agagaaggat 7081 ttggtattgg gtgaggggct ttctcccttt acctgcctct tcttgcttgc taatagtaag 7141 ttctttgtgc accttccacc acttctgagc cactactatt caagtagaga tttgccccaa 7201 cacattaact ttttccttgg agatttatat ggtcctgcat tttgtcctgt gctcacaatg 7261 tgaagtgtct tctgtattca aatcaaaaaa taatatattt aaggtatata agtgtgaatc 7321 tcctataatg atggaagaag aggttctctt gtcttagata gaaaagagcc ttctccaaga 7381 gcaatgtcaa aacttgggct gtcatctttg agctgtttac caaaatacag accattattg 7441 aagaaaaaca aattatctat tttgttttcc cccatctaac atgatagtgc ccccaaccag 7501 gttgtagcat tgccttttaa aagagactca ctcactctta gtttttaaga actggaaatt 7561 tcccatcctc agatccctta aaggatgaag agttggctgt acacttagcg gacttgcctc 7621 ttgtatgcaa ggactactga ttgaagtctg ttttgctgtg tctggttatg ttgtctgcac 7681 ttttatgaaa tcactacaat aggtctgcat tggaaatgac tattaatttg taaagaagta 7741 agttttatta aacactgtct agaaaaagaa agtgaagctg agaactcttc ctttattgtg 7801 catttatatt ttctgctgaa ttccggtagt tccctttaaa gtcatgttga ctaatgtttt 7861 cctccttgtt tgtattcaga tttccaaaat ttcactcata caagggaaga gactccattt 7921 agcttaacgg tagtctttag atcataagaa atatataaat tagtatgcac cttatctgcc 7981 tgttgtgggt ttcttaaact tgcacttcct acccacccaa agatagatat cctttaaaga 8041 aaataaaggc agagaattaa aactggggag ccatttacta tgtcaccatc actgttaact 8101 gtttcccagc aatctaaact ttttgaagtt tcagaggtgt attttttttt tgtatatatg 8161 tctgtgtgat tgtattgttt tgtttctaaa tatacaagga attctttaaa tagagaaaaa 8221 ggttaatcct cactgaaaca ccaggatgcc cactggatat actaatctga acatctgtag 8281 gtagtttgtc atgaaaaagt ggagagaaga tgagactttt gaatgaatga aaaagggtat 8341 cttgataccc agaattcccc ccaaagtacg ggtaattcaa cctgcacagt tttctttcac 8401 tcaaagtgtt cagcacttgt gagtgaaaaa tcatgtaatt atctgtaaat atgtagctaa 8461 caaattgacc tagtttctgt atttttttgt ttttgtacta aagtttatag gtctgtgcca 8521 gctagagaga agttgctgtc attaccagtt gtggtcctag catctaaccc tgaaaccatc 8581 ctaggtgaca tttttagaat taatacttaa atgttaaaca gggggaaatg aagcttaatc 8641 atggtcaggt ttgagatctt ttgcagtgaa ataattttat ttaatataaa tgatcacatg 8701 tcctcaatca tgaatgaggt agggagcctc tctcccccag tggccatgtt tacaaaagtg 8761 tgttttgtct ataaagtgca agtgttttaa tgtttatgta aattatgcag gtgataacat 8821 ggtttggaac tgtttattgg gctctttaac tgaattttca aatgaaatga actatgctta 8881 ttgctggcac attgatccca tttctggaac atttttccta tttccagagt tacatatgtt 8941 cttttgtcat tacccaattt aacctccctt tctctgatat gccttgtagc caaagtatta 9001 aaggctgatg aacatagaca agggaaatgc atttcttaga aatccgtgaa ccctcagttg 9061 tatgctttca gtactcgtgt taatatgttt ctatggcaac tctgaggtca gtggtttaga 9121 aatgagatac cagtgttaat gaaaagtgtg tgctctttgc ttttgcatgg cttggcttag 9181 tatccaaggt atattagggc cacttgaaag catgaagacc agttatatag ggaacaggtt 9241 tctctcagtg gcacattttg ctttttctga gccccaaata cattgcctgg gcatgaacat 9301 tgttaccgta aattgcacat ggtcatggac tgaattatgt gactttaaag gatgtaactg 9361 cccaacattt gcagattctg ggtggtctat gtgaccattt gtctcgtatc caaaaacccc 9421 ggggctattg gaacccttcc aacacttttt cctttgtcat agacaagttt atatataact 9481 taccaagatg ttggctgtcc tggtgtattg ccagacagct ctcttttggt tcccattcca 9541 aatgtgctgc tgtccttctt tgcatttcac aatatcaaag aaaccaccac ccttcttcct 9601 aacagcattt tatgcctttt attccacatt aaatgggaat tgtgcctact taggagtgcc 9661 cctccaatta attacatgtg tccaagaata atccaagcta gagacacaag gtgggaaaac 9721 atttcaaaaa aaaaaagtcc tcttaaggcc agtaatttat ctgaaaaggt attttatcac 9781 accttgacac cttatatatg agcctattag gagctgcagg tggtttcata gggtaaaatc 9841 caagaaaaga gaaggatgtg tggggtttct attagaagat aattttgttc tcattttacc 9901 ttttctttta tgatccttct ctgctagaac aggttaattc tccaaatttg ttttgttttg 9961 ttttgttatt ttttagggaa ctcttttgca aaagcaatgg tcggatgtaa ataacattta 10021 aagtatagtg cacataactt ccccggactg ttccaatctg ataatttgta aatgctttag 10081 agttttttta attaacactt gtgttgctaa attctattta tgtaagtctg ctaaagtttt 10141 ttagcccact taaaacttaa gacaaccatt taaaataatg gatgggttac tatgagcaat 10201 ttcgctttca gaaccccctt gttttagtat atgaaaaagc ctaatgcgca ttaatgaggt 10261 tgaagagact atgagaaata tgtatagtgt atattttaaa acagctttgc ttgtattgtg 10321 aagatttaaa aacaaacttg agatttttaa cgtaactatt aacacagttt taacataagt 10381 tatcccactg ggtttaagag catcttgaat gtataatcct ttttgtaacc caggttggtt 10441 tctactttta ccagtcaccc aaacatattt atgtttttag ttttatgtac tcatttccct 10501 ttgttttcct caaacagcat gatttttttg cacatgtaga aattttttaa aagaaagaaa 10561 ttagtacatc attttctctg gattttcttc acttccctct tcctttctac taactccttc 10621 cttaaaggcc atatcactcc atttgcatta tttgtgcaaa tgccagggtt ggtttttatt 10681 tttatttttg ctatttacct aaaaaaagaa aatgcttcag tcaattgctt ttttatttaa 10741 aaaaaaaaag aaaaaaagct gtaaccttat catttctgag tagaccattg agcgatgaat 10801 gcacacctgt agtagcccag gaccagctgt ggtggctaaa gggaatatgt taattaagca 10861 agaggttctt ttctaaaagt ggtatctgtt atccacaatg tattttagtt attcccacaa 10921 gtcaggggtc cagataaaat gagggttatc agctaactga tatgctatca ttgaggttca 10981 tcaatgaatt tgtacatttc tagttccctt tggtgaaggg aaaaatgatg attttgcaag 11041 acctagattt tggcttggtt tcttgcctcc ttttttggca gccttcatct tctcatctcc 11101 caaaccccct gagcccgtag ggttttcata gtggacaaag aacttgtggt cttttaaaac 11161 tgggactgat acttttttga gagagtatcg tgtcgaaagt gtgatgttct accactttac 11221 caataactaa ttttaaatac acattgtcct ctcgattttt ggaccaaaca gacgctcaca 11281 gtggaggctt atcaagggtt gcattgggga agaagcctct ccctctctgt cagcaccagc 11341 tggtaaaggt gactgtacag atgtgcattt tccttttggt ataaatggtc cacagcacta 11401 actggtaagg cttattgtac agtatattgt cagtattctt ctggttcagc ataccttata 11461 gttcatatat aacctgtatt aattgtatag attgtgcatt aaaagctgtt accaagttgt 11521 cagaacataa gagcgaaaac aaggtcatat gtaatatttt gtttgtaagt atcctttgta 11581 tcatagcaaa ggaaatgttt aaaaaaatca actgtaataa agtaatttta gtacacaaaa 11641 aaaaaaaaaa aa

An exemplary human PSG7 amino acid sequence is set forth below (SEQ ID NO: 196; GenBank Accession No: NP_002774.2, Version 2, incorporated herein by reference):

1 mgplsappct ghitwkglll tasllnfwnp pttaqvtiea qppkvsegkd vlllvhnlpq 61 nltgyiwykg qirdlyhyvt syivdgqiik ygpaysgret vysnaslliq nvtqedtgsy 121 tlhiikrgdg tggvtgrftf tlyletpkps isssnfnpre ateaviltcd petpdasylw 181 wmngqslpmt hslqlsetnr tlylfgvtny tagpyeceir npvsasrsdp vtlnllpklp 241 kpyitinnln prenkdvstf tcepksenyt yiwwlngqsl pvsprvkrri enrililpsv 301 trnetgpyqc eirdryggir sdpvtlnvly gpdlpriyps ftyyhsgqnl ylscfadsnp 361 paqyswting kfqlsgqkls ipqittkhsg lyacsvrnsa tgkessksvt vrvsdwtlp

An exemplary human PSG7 nucleic acid sequence is set forth below (SEQ ID NO: 197; GenBank Accession No: U18467.1, Version 1, incorporated herein by reference):

1 attcgggcct aggctcatct ccacagagga gaacacgcag ggagcagaga ccatggggcc 61 cctctcagcc cctccctgca cacagcatat aacctggaaa gggctcctgc tcacagcatc 121 acttttaaac ttctggaacc cgcccaccac agcccaagtc acgattgaag cccagccacc 181 aaaagtttct gaggggaagg atgttcttct acttgtccac aatttgcccc agaatcttac 241 tggctacatc tggtacaaag gacaaatcag ggacctctac cattatgtta catcatatgt 301 agtagacggt caaataatta aatatgggcc tgcatacagt ggacgagaaa cagtatattc 361 caatgcatcc ctgctgatcc agaatgtcac ccaggaagac acaggatcct acactttaca 421 catcataaag cgaggtgatg ggactggagg agtaactgga cgtttcacct tcaccttata 481 cctggagact cccaaaccct ccatctccag cagcaatttc aaccccaggg aggccacgga 541 ggctgtgatc ttaacctgtg atcctgagac tccagatgca agctacctgt ggtggatgaa 601 tggtcagagc ctccctatga ctcacagctt gcagctgtct gaaaccaaca ggaccctcta 661 cctatttggt gtcacaaact atactgcagg accctatgaa tgtgaaatac ggaacccagt 721 gagtgccagc cgcagtgacc cagtcaccct gaatctcctc ccgaagctgc ccaagcccta 781 catcaccatc aataacttaa accccaggga gaataaggat gtctcaacct tcacctgtga 841 acctaagagt gagaactaca cctacatttg gtggctaaat ggtcagagcc tcccggtcag 901 tcccagggta aagcgacgca ttgaaaacag gatcctcatt ctacccagtg tcacgagaaa 961 tgaaacagga ccctatcaat gtgaaatacg ggaccgatat ggtggcatcc gcagtgaccc 1021 agtcaccctg aatgtcctct atggtccaga cctccccaga atttaccctt cgttcaccta 1081 ttaccattca ggacaaaacc tctacttgtc ctgctttgcg gactctaacc caccggcaca 1141 gtattcttgg acaattaatg ggaagtttca gctatcagga caaaagcttt ctatccccca 1201 gattactaca aagcatagcg ggctctatgc ttgctctgtt cgtaactcag ccactggcaa 1261 ggaaagctcc aaatccgtga cagtcagagt ctctgactgg acattaccct gaattctact 1321 agttcctcca attccatctt ctcccatgga acctcaaaga gcaagaccca ctctgttcca 1381 gaagccctat aagtcagagt tggacaactc aatgtaaatt tcatgggaaa atccttgtac 1441 ctgatgtctg agccactcag aactcaccaa aatgttcaac accataacaa cagctgctca 1501 aactgtaaac aaggaaaaca agttgatgac ttcacactgt ggacagtttt tcccaagatg 1561 tcagaataag actccccatc atgatgaggc tctcacccct cttagctgtc cttgcttgtg 1621 cctgcctctt tcacttggca ggataatgca gtcattagaa tttcacatgt agtataggag 1681 cttctgaggg taacaacaga gtgtcagata tgtcatctca acctcaaact tttacataac 1741 atctcaggag gaaatgtggc tctctccatc ttgcatacag ggctcccaat agaaatgaac 1801 acagagatat tgcctgtgtg tttgcagaga agatggtttc tataaagagt aggaaagctg 1861 aaattatagt agagtcccct ttaaatgcac attgtgtgga tggctctcac catttcctaa 1921 gagatacatt gtaaaacgtg acagtaagac tgattctagc agaataaaac atgtactaca 1981 tttgctaaa

An exemplary human PSG8 amino acid sequence is set forth below (SEQ ID NO: 198; GenBank Accession No: AAI37501.1, Version 1, incorporated herein by reference):

1 mgllsappct qritwkglll tasllnfwnp pttaqvtiea qptkvsegkd vlllvhnlpq 61 nltgyiwykg qirdlyhyit syvvdgqiii ygpaysgret iysnaslliq nvtqedagsy 121 tlhiimggde nrgvtghftf tlyletpkps isssklnpre ameavsltcd petpdasylw 181 wmngqslpms hrlqlsetnr tlfllgvtky tagpyeceir npvsasrsdp ftlnllpklp 241 kpyitinnlk prenkdvlnf tcepksenyt yiwwlngqsl pvsprvkrpi enrililpsv 301 trnetgpyqc eirdqyggir sypvtlnvly gpdlpriyps ftyyrsgevl ylscsadsnp 361 paqyswting kfqlsgqklf ipqittkhsg lyacsvrnsa tgkessksmt vkvsgkripv 421 slaigi

An exemplary human PSG8 nucleic acid sequence is set forth below (SEQ ID NO: 199; GenBank Accession No: BC142628.1, Version 1, incorporated herein by reference):

1 ggacagcact gctgagagct gtgctcagga agcttctgga tcctaggctc atctccacag 61 aggagaacac acagacagca gagaccatgg ggctcctctc agcccctccc tgcacacagc 121 gcatcacctg gaaggggctc ctgctcacag catcactttt aaacttctgg aacccaccca 181 cgactgccca agtcacgatt gaagcccagc caaccaaagt ttctgagggg aaggatgttc 241 ttctacttgt ccacaatttg ccccagaatc ttactggcta catctggtac aaagggcaaa 301 tcagggacct ctaccattac attacatcat atgtagtaga cggtcaaata attatatatg 361 ggcctgcata cagtggacga gaaacaatat attccaatgc atccctgctg atccagaatg 421 tcacccagga agacgcagga tcctacacct tacacatcat aatgggaggt gatgagaata 481 gaggagtaac tggacatttc accttcacct tatatctgga gactcccaag ccctccatct 541 ccagcagcaa attaaacccc agggaggcca tggaggctgt gagcttaacc tgtgatcctg 601 agactccgga cgcaagctac ctgtggtgga tgaatggtca gagcctccct atgtctcaca 661 ggttgcagtt gtctgaaacc aacaggaccc tctttctatt gggtgtcaca aagtacactg 721 caggacccta tgaatgtgaa atacggaacc cagtgagtgc cagccgcagt gacccattca 781 ccctgaatct cctcccgaag ctgcccaagc cctacatcac catcaacaac ttaaaaccca 841 gggagaataa ggatgtctta aacttcacct gtgaacctaa gagtgagaac tacacctaca 901 tttggtggct aaatggtcag agcctcccgg tcagtcccag ggtaaagcga cccattgaaa 961 acaggatcct cattctaccc agtgtcacga gaaatgaaac aggaccctat caatgtgaaa 1021 taagggacca atatggtggc atccgcagtt acccagtcac cctgaatgtc ctctatggtc 1081 cagacctccc cagaatttac ccttcattca cctattaccg ttcaggagaa gtcctctact 1141 tgtcctgttc tgcggactct aacccaccgg cacagtattc ttggacaatt aatgggaagt 1201 ttcagctatc aggacaaaag ctctttatcc cccaaattac tacaaagcat agcgggctct 1261 atgcttgctc tgttcgtaac tcagccactg gcaaggaaag ctccaaatcc atgacagtaa 1321 aagtctctga ctggacatta ccctgaattc tactagttcc tccaattcca ttttcttcca 1381 tggaatcgct aagaaaaaga cccactctgt tccagaagcc ctataagctg gaggtggaca 1441 actcaatgta aatttcatgg gaaaaccctt gtacctgaag cgtgagccac tcagaactca 1501 ctaaaatgtt cgacaccata acaacagatg ctcaaactgt aaaccaggac aacaagtgga 1561 tgacttcaca ctgtggacag tttttcccaa gatgtcagaa caagactccc catcatgatg 1621 aggctctcac ccctcttaac tgtccttgct catgcctgcc tctttcactt ggcaggataa 1681 tgcagtcatt agaatttcac atgtagtagc ttctgagggt aacaatagag tgtcagatat 1741 gtcatctcaa cccaaacttt tacataacat ctcaggggga aatgtggctc tctccacctt 1801 gcatacagga ctcccaatag aaatgaacac agagatattg cccgtgtgtt tgcagataag 1861 atggtttcta tgaagaggta ggaaagctga aattataata gagtcccctt taaatgcaca 1921 ttctgtggat ggctctcgcc atttcctaag agatacattg taaaatgtga cagtaatact 1981 gattctagca gaataaaaca tgtaccacat ttgctaatac aaaaaaaaaa aaaaaaaaaa 2041 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2101 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaa

An exemplary human PSG9 amino acid sequence is set forth below (SEQ ID NO: 200; GenBank Accession No: AAH20759.1, Version 1, incorporated herein by reference):

1 mgplpapsct qritwkglll tasllnfwnp pttaevtiea qppkvsegkd vlllvhnlpq 61 nlpgyfwykg emtdlyhyii syivdgkiii ygpaysgret vysnaslliq nvtrkdagty 121 tlhiikrgde treeirhftf tlyletpkpy isssnlnpre ameavrlicd petldasylw 181 wmngqslpvt hrlqlsktnr tlylfgvtky iagpyeceir npvsasrsdp vtlnllpklp 241 ipyitinnln prenkdvlaf tcepksenyt yiwwlngqsl pvspgvkrpi enrililpsv 301 trnetgpyqc eiqdrygglr snpvilnvly gpdlpriyps ftyyrsgenl dlscftesnp 361 paeyfwting kfqqsgqklf ipqitrnhsg lyacsvhnsa tgkeisksmt vkvsgpchgd 421 ltesqs

An exemplary human PSG9 nucleic acid sequence is set forth below (SEQ ID NO: 201; GenBank Accession No: BC020759.1, Version 1, incorporated herein by reference):

1 agaaggagga aggacagcac agctgacagc cgtgctcaga cagcttctgg atcccaggct 61 catctccaca gaggagaaca cacaggcagc agagaccatg gggcccctcc cagccccttc 121 ctgcacacag cgcatcacct ggaaggggct cctgctcaca gcatcacttt taaacttctg 181 gaacccgccc accactgccg aagtcacgat tgaagcccag ccacccaaag tttctgaggg 241 gaaggatgtt cttctacttg tccacaattt gccccagaat cttcctggct acttctggta 301 caaaggggaa atgacggacc tctaccatta cattatatcg tatatagttg atggtaaaat 361 aattatatat gggcctgcat acagtggaag agaaacagta tattccaacg catccctgct 421 gatccagaat gtcacccgga aggatgcagg aacctacacc ttacacatca taaagcgagg 481 tgatgagact agagaagaaa ttcgacattt caccttcacc ttatacttgg agactcccaa 541 gccctacatc tccagcagca acttaaaccc cagggaggcc atggaggctg tgcgcttaat 601 ctgtgatcct gagactctgg acgcaagcta cctatggtgg atgaatggtc agagcctccc 661 tgtgactcac aggttgcagc tgtccaaaac caacaggacc ctctatctat ttggtgtcac 721 aaagtatatt gcaggaccct atgaatgtga aatacggaac ccagtgagtg ccagtcgcag 781 tgacccagtc accctgaatc tcctcccgaa gctgcccatc ccctacatca ccatcaacaa 841 cttaaacccc agggagaata aggatgtctt agccttcacc tgtgaaccta agagtgagaa 901 ctacacctac atttggtggc taaacggtca gagcctcccc gtcagtcccg gggtaaagcg 961 acccattgaa aacaggatac tcattctacc cagtgtcacg agaaatgaaa caggacccta 1021 tcaatgtgaa atacaggacc gatatggtgg cctccgcagt aacccagtca tcctaaatgt 1081 cctctatggt ccagacctcc ccagaattta cccttcattc acctattacc gttcaggaga 1141 aaacctcgac ttgtcctgct tcacggaatc taacccaccg gcagagtatt tttggacaat 1201 taatgggaag tttcagcaat caggacaaaa gctctttatc ccccaaatta ctagaaatca 1261 tagcgggctc tatgcttgct ctgttcataa ctcagccact ggcaaggaaa tctccaaatc 1321 catgacagtc aaagtctctg gtccctgcca tggagacctg acagagtctc agtcatgact 1381 gcaacaactg agacactgag aaaaagaaca ggctgatacc ttcatgaaat tcaagacaaa 1441 gaagaaaaaa actcaatgtt attggactaa ataatcaaaa ggataatgtt ttcataattt 1501 tttattggaa aatgtgctga ttctttgaat gttttattct ccagatttat gaactttttt 1561 tcttcagcaa ttggtaaagt atacttttat aaacaaaaat tgaaatattt gcttttgctg 1621 tctatctgaa tgccccagaa ttgtgaaact attcatgagt attcataggt ttatggtaat 1681 aaagttattt gcacatgttc caaaaaaaaa aaaaaaaaaa aaaaaaaaaa a

An exemplary human PSG11 amino acid sequence is set forth below (SEQ ID NO: 202 GenBank Accession No: AAA60203.1, Version 1, incorporated herein by reference):

1 mgpfpapsct qritwkglll tasllnfwnp pttaevtiea qppkvsegkd vlllvhnlpq 61 nlpgyfwykg emtdlyhyii syivdgkiii ygpaysgret vysnaslliq nvtrkdagty 121 tlhiikrgde treeirhftf tlyletpkpy isssnlnpre ameavrlicd petldasylw 181 wmngqslpvt hrlqlsktnr tlylfgvtky iagpyeceir npvsairsdp vtlnllpklp 241 ipyitinnln prenkdvlaf tcepksenyt yiwwlngqsl pvspgvkrpi enrililpsv 301 trnetgpyqc eirdrygglr snpvilnvly gpdlpriyps ftyyrsgenl dlscftesnp 361 paeyfwting kfqqsgqklf ipqitrnhsg lyacsvhnsa tgkeisksmt vkvsgpchgd 421 ltesqs

An exemplary human PSG11 nucleic acid sequence is set forth below (SEQ ID NO: 203; GenBank Accession No: M58591.1, Version 1, incorporated herein by reference):

1 cagccgtgct cagacagctt ctggatccta ggctcatctc cacagaggag aacacgcagg 61 cagcagagac catggggccc ttcccagccc cttcctgcac acagcgcatc acctggaagg 121 ggctcctgct cacagcatca cttttaaact tctggaaccc gcccaccact gccgaagtca 181 cgattgaagc ccagccaccc aaagtttctg aggggaagga tgttcttcta cttgtccaca 241 atttgcccca gaatcttcct ggctacttct ggtacaaagg ggaaatgacg gacctctacc 301 attacattat atcgtatata gttgatggta aaataattat atatgggcct gcatacagtg 361 gaagagaaac agtatattcc aacgcatccc tgctgatcca gaatgtcacc cggaaggatg 421 caggaaccta caccttacac atcataaagc gaggtgatga gactagagaa gaaattcgac 481 atttcacctt caccttatac ttggagactc ccaagcccta catctccagc agcaacttaa 541 accccaggga ggccatggag gctgtgcgct taatctgtga tcctgagact ctggacgcaa 601 gctacctatg gtggatgaat ggtcagagcc tccctgtgac tcacaggttg cagctgtcca 661 aaaccaacag gaccctctat ctatttggtg tcacaaagta tattgcagga ccctatgaat 721 gtgaaatacg gaacccagtg agtgccattc gcagtgaccc agtcaccctg aatctcctcc 781 cgaagctgcc catcccctac atcaccatca acaacttaaa ccccagggag aataaggatg 841 tcttagcctt cacctgtgaa cctaagagtg agaactacac ctacatttgg tggctaaacg 901 gtcagagcct ccccgtcagt cccggggtaa agcgacccat tgaaaacagg atactcattc 961 tacccagtgt cacgagaaat gaaacaggac cctatcaatg tgaaatacgg gaccgatatg 1021 gtggcctccg cagtaaccca gtcatcctaa atgtcctcta tggtccagac ctccccagaa 1081 tttacccttc attcacctat taccgttcag gagaaaacct cgacttgtcc tgcttcacgg 1141 aatctaaccc accggcagag tatttttgga caattaatgg gaagtttcag caatcaggac 1201 aaaagctctt tatcccccaa attactagaa atcatagcgg gctctatgct tgctctgttc 1261 ataactcagc cactggcaag gaaatctcca aatccatgac agtcaaagtc tctggtccct 1321 gccatggaga cctgacagag tctcagtcat gactgcaaca actgagacac tgagaaaaag 1381 aacaggctga taccttcatg aaattcaaga caaagaagaa aaaaactcaa tgttattgga 1441 ctaaataatc aaaaggataa tgttttcata attttttatt ggaaaatgtg ctgattcttt 1501 gaatgtttta ttctccagat ttatgaactt tttttcttca gcaattggta aagtatactt 1561 ttgtaaacaa aaattgaaat atttgctttt gctgtctatc tgaatgcccc agaattgtga 1621 aactattcat gagtattcat aggtttatgg taataaagtt atttgcacat gttccgta

An exemplary human miR-185 nucleic acid sequence is set forth below (SEQ ID NO: 204; GenBank Accession No: NR_029706.1, Version 1, incorporated herein by reference):

1 agggggcgag ggattggaga gaaaggcagt tcctgatggt cccctcccca ggggctggct 61 ttcctctggt ccttccctcc ca

An exemplary human miR-513a2 nucleic acid sequence is set forth below (SEQ ID NO: 205; GenBank Accession No: LM609506.1, Version 1, incorporated herein by reference):

1 ggatgccaca ttcagccatt cagtgtgcag tgcctttcac agggaggtgt catttatgtg 61 aactaaaata taaatttcac ctttctgaga agggtaatgt acagcatgca ctgcatatgt 121 ggtgtcc

An exemplary human HMGB1 amino acid sequence is set forth below (SEQ ID NO: 210 GenBank Accession No: CAG33144.1, Version 1, incorporated herein by reference):

1 mgkgdpkkpr gkmssyaffv qtcreehkkk hpdasvnfse fskkcserwk tmsakekgkf 61 edmakadkar yeremktyip pkgetkkkfk dpnapkrpps afflfcseyr pkikgehpgl 121 sigdvakklg emwnntaadd kqpyekkaak lkekyekdia ayrakgkpda akkgvvkaek 181 skkkkeeeed eedeedeeee edeededeee ddddd

An exemplary human HMGB1 nucleic acid sequence is set forth below (SEQ ID NO: 211; GenBank Accession No: NM_001313893.1, Version 1, incorporated herein by reference):

1 tttctgcgga gggattacgc tgacgaaaga gacctgcttg cgcgtcgctg ttccgtggtc 61 cgcgcgagcg tggtcgggag ccgctggttc ctggggtgac ccgcggaggt gggagaggga 121 agggcttccg aagccggcgg gggtgccatg gaccctctcc gccggcgcgg ccttcacagc 181 tgggccgcgc cgggcatccg tagtccgctc tcccaaagcc tcggtggagc tgaagctgcc 241 acagagtgca tgttcacaaa gggtcatcac acacggagct gcccctccct gtctccctag 301 agcccatctt cgaggccagg ggcttttcta ccaggattct ggggtgtttc tcctcctttc 361 ctccctccca gatcttctca cggtaagggg agcagcgaaa gcgcagggac tttgcattcc 421 acgacccgtt ctgactagtc aacagccgat ctgtccctgc tgctctaatt ccagctgccc 481 tgccttgttt taacttcaga gaaaggggga gttctcattt gataagttta agcctttgct 541 ttcgtaggaa ggtcatgtgg cttaagggac atcgtgaccg cgtatgctat ttctgcctgt 601 gcattctaaa tcttgggggc agcatattcc agaagtcctt ttggtcgatt ggttctgtgt 661 cctaggataa caatttgtag tttctgacca tttctttaca gaaaaaccac aattggtatt 721 ttggactgcg gggtttttta gtggtctcaa actaaatgat tatattctgg aataatgctg 781 acaatttgga tagggtggtg tggaggaaac aagtctcgtg tagaagaaat tatttagtaa 841 aaaggatttt agtttttggt acttctgaat gcaaatggcc aaggaatcca gcagtttgtt 901 ggggtttctc cagacaaaaa taggctgaaa aataactaaa catgggcaaa ggagatccta 961 agaagccgag aggcaaaatg tcatcatatg cattttttgt gcaaacttgt cgggaggagc 1021 ataagaagaa gcacccagat gcttcagtca acttctcaga gttttctaag aagtgctcag 1081 agaggtggaa gaccatgtct gctaaagaga aaggaaaatt tgaagatatg gcaaaagcgg 1141 acaaggcccg ttatgaaaga gaaatgaaaa cctatatccc tcccaaaggg gagacaaaaa 1201 agaagttcaa ggatcccaat gcacccaaga ggcctccttc ggccttcttc ctcttctgct 1261 ctgagtatcg cccaaaaatc aaaggagaac atcctggcct gtccattggt gatgttgcga 1321 agaaactggg agagatgtgg aataacactg ctgcagatga caagcagcct tatgaaaaga 1381 aggctgcgaa gctgaaggaa aaatacgaaa aggatattgc tgcatatcga gctaaaggaa 1441 agcctgatgc agcaaaaaag ggagttgtca aggctgaaaa aagcaagaaa aagaaggaag 1501 aggaggaaga tgaggaagat gaagaggatg aggaggagga ggaagatgaa gaagatgaag 1561 atgaagaaga agatgatgat gatgaataag ttggttctag cgcagttttt tttttcttgt 1621 ctataaagca tttaaccccc ctgtacacaa ctcactcctt ttaaagaaaa aaattgaaat 1681 gtaaggctgt gtaagatttg tttttaaact gtacagtgtc tttttttgta tagttaacac 1741 actaccgaat gtgtctttag atagccctgt cctggtggta ttttcaatag ccactaacct 1801 tgcctggtac agtatggggg ttgtaaattg gcatggaaat ttaaagcagg ttcttgttgg 1861 tgcacagcac aaattagtta tatatgggga tggtagtttt ttcatcttca gttgtctctg 1921 atgcagctta tacgaaataa ttgttgttct gttaactgaa taccactctg taattgcaaa 1981 aaaaaaaaaa aagttgcagc tgttttgttg acattctgaa tgcttctaag taaatacaat 2041 tttttttatt agtattgttg tccttttcat aggtctgaaa tttttcttct tgaggggaag 2101 ctagtctttt gcttttgccc attttgaatc acatgaatta ttacagtgtt tatcctttca 2161 tatagttagc taataaaaag cttttgtcta cacaccctgc atatcataat gggggtaaag 2221 ttaagttgag atagttttca tccataactg aacatccaaa atcttgatca gttaagaaat 2281 ttcacatagc ccacttacat ttacaaactg aagagtaatc aatctactca aagcatggga 2341 ttattagaat caaacatttt gaaagtctgt ccttgaagga ctaatagaaa agtatgttct 2401 aacctttaca tgaggactct attctttaac tcccattacc atgtaatggc agttatattt 2461 tgcagttccc acattaaaga agacctgaga atgtatcccc aaaagcgtga gcttaaaata 2521 caagactgcc atattaaatt ttttgttgac attagtctca gtgaagacta tgaaaatgct 2581 ggctatagat gtcttttccc atttatctaa atatggactg ctcaggaaac gagactttcc 2641 attacaagta tttttaatta attgggccag cttttcaaac aaagatgcca cattcaaaat 2701 agggtatatt ttcctatatt acggtttgcc cctttataaa tccaagtaga taggaagaaa 2761 gaagacaaac tttgcatctc agtatgaatt attcaattta tttgaatgat ttttctttac 2821 aaaacaaact cattcattag tcatgtttat ctgcttagga gtttagggaa caatttggca 2881 attttgtggt tttcgagatt atcgttttct taaagtgcca gtattttaaa atagcgttct 2941 tgtaatttta cacgcttttg tgatggagtg ctgttttgtt atataattta gacttggatt 3001 ctttccattt gcatttgttt atgtaatttc aggaggaata ctgaacatct gagtcctgga 3061 tgatactaat aaactaataa ttgcagaggt tttaaatact agttaaatgg ctttcactta 3121 agaacttaag attttgttac atatttttaa atcttgtttc taataatacc tcttagcagt 3181 accttttaaa taagtataag ggatggcaaa gtttttccct ttaaaaatac tcactttatg 3241 cttataaata ggttaatggg ctgataaaag gttttgtcaa acattgcaag tattcggtgc 3301 tatatataaa ggaggaaaaa ctagttttac tttcagaatg atttaaacaa gatttttaaa 3361 aacaagatac atgcaagcga acagcagggt tagtgatagg ctgcaattgt gtcgaacatc 3421 agattttttg ttaagaggag caaatgactc aatctgattt agatggaagt ttctactgta 3481 tagaaatcac cattaatcac caacattaat aattctgatc catttaaaat gaattctggc 3541 tcaaggagaa tttgtaactt tagtaggtac gtcatgacaa ctaccatttt tttaagatgt 3601 tgagaatggg aacagttttt ttagggttta ttcttgacca cagatcttaa gaaaatggac 3661 aaaacccctc ttcaatctga agattagtat ggtttggtgt tctaacagta tcccctagaa 3721 gttggatgtc taaaactcaa gtaaatggaa gtgggaggca atttagataa gtgtaaagcc 3781 ttgtaactga agatgatttt ttttagaaag tgtatagaaa ctattttaat gccaagatag 3841 ttacagtgct gtggggttta aagactttgt tgacatcaag aaaagactaa atctataatt 3901 aattgggcca acttttaaaa tgaagatgct ttttaaaact aatgaactaa gatgtataaa 3961 tcttagtttt tttgtatttt aaagataggc atatggcata ttgattaacg agtcaaattt 4021 cctaactttg ctgtgcaaag gttgagagct attgctgatt agttaccaca gttctgatga 4081 tcgtcccatc acagtgttgt taatgtttgc tgtatttatt aattttctta aagtgaaatc 4141 tgaaaaatga aatttgtgtg tcctgtgtac ccgaggggta atgattaaat gataaagata 4201 agaaaagcgc ccatgtaaca caaactgcca ttcaacaggt atttccctta ctacctaagg 4261 aattgtaacc attgctcaga cattgtagga tttaactatg ttgaaaacta caggagaggc 4321 cgggcgcagt ggctcacgcc tgtaatccca gcactttggg aggccaaggc gggcagatca 4381 cgaggtcagg agattgagac catcctggct aacgtggtga aaccccgcct ctactaaaaa 4441 tacaaaaaat tagccaagcg tggtgctggg cgcctgtagt cccagtaact caggaggctg 4501 aggcaggaga atggcgtgaa cccgggaggc ggaggttgca gtgagccgag attgtgccac 4561 tgcactccag cctgggtgac agagcaagac tccatctcaa aaaaaaaaaa aaaacacagg 4621 agagacaact ggtttttgaa tgaaatacat gggtactgcc ttgcttgaca tcacatagtc 4681 cttgatgaaa gttcacattt aggtctgctt ggtacaatac gcctcctaaa aaggtccttg 4741 atgaaagttc acatttaggt ctgcttggta caacacgcct cctgaaaggg tctgatagct 4801 ttcagtagca gtaagacact tgcatgtgat ggtaaggtat ctgcaaattt gcacacaccg 4861 tacacagctt aagtcttaga attaacttgc taaaatgtga gcctttggta attaggctgt 4921 tttattaggg agtgtgataa tatttgaatt tcttttcata tttgtgcttt gtgtcatttt 4981 caaatgaccc ttgaaatgta ttttaaaagt agataaaagc cagaaagtga

Pharmaceutical Therapeutics

For therapeutic uses, the compositions or agents described herein may be administered systemically, for example, formulated in a pharmaceutically-acceptable buffer such as physiological saline. Preferable routes of administration include, for example, subcutaneous, intravenous, interperitoneally, intramuscular, or intradermal injections that provide continuous, sustained levels of the drug in the patient. Treatment of human patients or other animals will be carried out using a therapeutically effective amount of a therapeutic identified herein in a physiologically-acceptable carrier. Suitable carriers and their formulation are described, for example, in Remington's Pharmaceutical Sciences by E. W. Martin. The amount of the therapeutic agent to be administered varies depending upon the manner of administration, the age and body weight of the patient, and with the clinical symptoms of the neoplasia, i.e., the melanoma. Generally, amounts will be in the range of those used for other agents used in the treatment of other diseases associated with neoplasia, although in certain instances lower amounts will be needed because of the increased specificity of the compound. For example, a therapeutic compound is administered at a dosage that is cytotoxic to a neoplastic cell.

Formulation of Pharmaceutical Compositions

The administration of a compound or a combination of compounds for the treatment of a neoplasia, e.g., a melanoma, may be by any suitable means that results in a concentration of the therapeutic that, combined with other components, is effective in ameliorating, reducing, or stabilizing a neoplasia. The compound may be contained in any appropriate amount in any suitable carrier substance, and is generally present in an amount of 1-95% by weight of the total weight of the composition. The composition may be provided in a dosage form that is suitable for parenteral (e.g., subcutaneously, intravenously, intramuscularly, or intraperitoneally) administration route. The pharmaceutical compositions may be formulated according to conventional pharmaceutical practice (see, e.g., Remington: The Science and Practice of Pharmacy (20th ed.), ed. A. R. Gennaro, Lippincott Williams & Wilkins, 2000 and Encyclopedia of Pharmaceutical Technology, eds. J. Swarbrick and J. C. Boylan, 1988-1999, Marcel Dekker, New York).

Human dosage amounts can initially be determined by extrapolating from the amount of compound used in mice, as a skilled artisan recognizes it is routine in the art to modify the dosage for humans compared to animal models. In certain embodiments it is envisioned that the dosage may vary from between about 1 μg compound/Kg body weight to about 5000 mg compound/Kg body weight; or from about 5 mg/Kg body weight to about 4000 mg/Kg body weight or from about 10 mg/Kg body weight to about 3000 mg/Kg body weight; or from about 50 mg/Kg body weight to about 2000 mg/Kg body weight; or from about 100 mg/Kg body weight to about 1000 mg/Kg body weight; or from about 150 mg/Kg body weight to about 500 mg/Kg body weight. In other cases, this dose may be about 1, 5, 10, 25, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1050, 1100, 1150, 1200, 1250, 1300, 1350, 1400, 1450, 1500, 1600, 1700, 1800, 1900, 2000, 2500, 3000, 3500, 4000, 4500, or 5000 mg/Kg body weight. In other aspects, it is envisaged that doses may be in the range of about 5 mg compound/Kg body to about 20 mg compound/Kg body. In other embodiments, the doses may be about 8, 10, 12, 14, 16 or 18 mg/Kg body weight. Of course, this dosage amount may be adjusted upward or downward, as is routinely done in such treatment protocols, depending on the results of the initial clinical trials and the needs of a particular patient.

Pharmaceutical compositions according to the invention may be formulated to release the active compound substantially immediately upon administration or at any predetermined time or time period after administration. The latter types of compositions are generally known as controlled release formulations, which include (i) formulations that create a substantially constant concentration of the drug within the body over an extended period of time; (ii) formulations that after a predetermined lag time create a substantially constant concentration of the drug within the body over an extended period of time; (iii) formulations that sustain action during a predetermined time period by maintaining a relatively, constant, effective level in the body with concomitant minimization of undesirable side effects associated with fluctuations in the plasma level of the active substance (sawtooth kinetic pattern); (iv) formulations that localize action by, e.g., spatial placement of a controlled release composition adjacent to or in contact with the thymus; (v) formulations that allow for convenient dosing, such that doses are administered, for example, once every one or two weeks; and (vi) formulations that target a neoplasia by using carriers or chemical derivatives to deliver the therapeutic agent to a particular cell type (e.g., neoplastic cell). For some applications, controlled release formulations obviate the need for frequent dosing during the day to sustain the plasma level at a therapeutic level.

Any of a number of strategies can be pursued in order to obtain controlled release in which the rate of release outweighs the rate of metabolism of the compound in question. In one example, controlled release is obtained by appropriate selection of various formulation parameters and ingredients, including, e.g., various types of controlled release compositions and coatings. Thus, the therapeutic is formulated with appropriate excipients into a pharmaceutical composition that, upon administration, releases the therapeutic in a controlled manner. Examples include single or multiple unit tablet or capsule compositions, oil solutions, suspensions, emulsions, microcapsules, microspheres, molecular complexes, nanoparticles, patches, and liposomes.

Parenteral Compositions

The pharmaceutical composition may be administered parenterally by injection, infusion or implantation (subcutaneous, intravenous, intramuscular, intraperitoneal, or the like) in dosage forms, formulations, or via suitable delivery devices or implants containing conventional, non-toxic pharmaceutically acceptable carriers and adjuvants. The formulation and preparation of such compositions are well known to those skilled in the art of pharmaceutical formulation. Formulations can be found in Remington: The Science and Practice of Pharmacy, supra.

Compositions for parenteral use may be provided in unit dosage forms (e.g., in single-dose ampoules), or in vials containing several doses and in which a suitable preservative may be added (see below). The composition may be in the form of a solution, a suspension, an emulsion, an infusion device, or a delivery device for implantation, or it may be presented as a dry powder to be reconstituted with water or another suitable vehicle before use. Apart from the active agent that reduces or ameliorates a neoplasia, the composition may include suitable parenterally acceptable carriers and/or excipients. The active therapeutic agent(s) may be incorporated into microspheres, microcapsules, nanoparticles, liposomes, or the like for controlled release. Furthermore, the composition may include suspending, solubilizing, stabilizing, pH-adjusting agents, tonicity adjusting agents, and/or dispersing, agents.

As indicated above, the pharmaceutical compositions according to the invention may be in the form suitable for sterile injection. To prepare such a composition, the suitable active antineoplastic therapeutic(s) are dissolved or suspended in a parenterally acceptable liquid vehicle. Among acceptable vehicles and solvents that may be employed are water, water adjusted to a suitable pH by addition of an appropriate amount of hydrochloric acid, sodium hydroxide or a suitable buffer, 1,3-butanediol, Ringer's solution, and isotonic sodium chloride solution and dextrose solution. The aqueous formulation may also contain one or more preservatives (e.g., methyl, ethyl or n-propyl p-hydroxybenzoate). In cases where one of the compounds is only sparingly or slightly soluble in water, a dissolution enhancing or solubilizing agent can be added, or the solvent may include 10-60% w/w of propylene glycol.

Controlled Release Parenteral Compositions

Controlled release parenteral compositions may be in form of aqueous suspensions, microspheres, microcapsules, magnetic microspheres, oil solutions, oil suspensions, or emulsions. Alternatively, the active drug may be incorporated in biocompatible carriers, liposomes, nanoparticles, implants, or infusion devices.

Materials for use in the preparation of microspheres and/or microcapsules are, e.g., biodegradable/bioerodible polymers such as polygalactin, poly-(isobutyl cyanoacrylate), poly(2-hydroxyethyl-L-glutam-nine) and, poly(lactic acid). Biocompatible carriers that may be used when formulating a controlled release parenteral formulation are carbohydrates (e.g., dextrans), proteins (e.g., albumin), lipoproteins, or antibodies. Materials for use in implants can be non-biodegradable (e.g., polydimethyl siloxane) or biodegradable (e.g., poly(caprolactone), poly(lactic acid), poly(glycolic acid) or poly(ortho esters) or combinations thereof).

Kits or Pharmaceutical Systems

The present compositions may be assembled into kits or pharmaceutical systems for use in ameliorating a neoplasia (e.g., melanoma). Kits or pharmaceutical systems according to this aspect of the invention comprise a carrier means, such as a box, carton, tube or the like, having in close confinement therein one or more container means, such as vials, tubes, ampoules, or bottles. The kits or pharmaceutical systems of the invention may also comprise associated instructions for using the agents of the invention.

The practice of the present invention employs, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry and immunology, which are well within the purview of the skilled artisan. Such techniques are explained fully in the literature, such as, “Molecular Cloning: A Laboratory Manual”, second edition (Sambrook, 1989); “Oligonucleotide Synthesis” (Gait, 1984); “Animal Cell Culture” (Freshney, 1987); “Methods in Enzymology” “Handbook of Experimental Immunology” (Weir, 1996); “Gene Transfer Vectors for Mammalian Cells” (Miller and Calos, 1987); “Current Protocols in Molecular Biology” (Ausubel, 1987); “PCR: The Polymerase Chain Reaction”, (Mullis, 1994); “Current Protocols in Immunology” (Coligan, 1991). These techniques are applicable to the production of the polynucleotides and polypeptides of the invention, and, as such, may be considered in making and practicing the invention. Particularly useful techniques for particular embodiments will be discussed in the sections that follow.

The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the assay, screening, and therapeutic methods of the invention, and are not intended to limit the scope of what the inventors regard as their invention.

Examples Example 1: Molecular Signatures of Resistance (No Benefit)

First, expression data from a previously published cohort of pre-ipilimumab treated melanoma patients (Cohort 1) was analyzed (Van Allen et al., 2015 Science, 350(6257):207-11, incorporated herein by reference). The patients were classified into three groups based on their post-treatment outcome: (i) patients who achieved complete or partial response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria or stable disease by RECIST criteria with overall survival greater than one year (“clinical benefit/CB;” n=13); (ii) patients who had progressive disease by RECIST criteria or stable disease with overall survival less than 1 year (“no benefit/NB;” n=22); and (iii) patients showing early progression on ipilimumab (progression-free survival (PFS)<6 months) with overall survival >2 years (“long-term survival with no clinical benefit/LTS;” n=5). The LTS group was removed from the differential expression analysis for three reasons: 1) their unique clinical course suggests a potentially different clinicobiology; 2) the small number of samples precludes any meaningful comparisons with the other two groups; and 3) the focus was purely on expression patterns distinguishing clear benefit from clear resistance. Therefore, an unbiased differential gene expression analysis was performed between the CB and NB groups. Because of the limited number of patients, the statistical stringency was relaxed in the unbiased differential expression analysis by forgoing multiple hypothesis correction. Using a cutoff of 2-fold difference between the absolute medians of the two groups (unadjusted Mann-Whitney p<0.05), 975 genes co-enriched in the ‘no benefit’ tumors (FIG. 1A) were identified.

Strikingly, 8 of the top 10 genes enriching 60-180 fold in ‘NB’ tumors clustered within a narrow 75 Kb region of chromosome Xq28 (FIG. 1A, FIG. 1B, FIG. 12A), representing 0.0023% of the human genome. All 8 genes (MAGEA3, MAGEA6, CSAG1, MAGEA12, MAGEA2, CSAG2, and CSAG3 and CSAG4) encoded cancer-germline antigens (CGAs), a large family of 140 members notable for their restricted expression in testis and placenta but re-expression across many tumor types. While many subclusters of CGA's are located on Xq28, this particular subcluster has demonstrated an expression pattern independent of surrounding CGA clusters; in fact, the synchronous expression of these 8 clustered genes may be driven by their unique inverted repeat DNA structure. 14/22 NB tumors showed upregulation of at least one of these 8 CGA's versus 2/13 CB tumors (p=0.0125).

In addition to the CGA cluster on Xq28, increased expression of additional CGAs was identified in NB samples, though none were as highly expressed as those at the CRMA locus (Table 2, FIG. 14). Moreover, previously described melanoma antigens, such as NY-ESO-1, whose humoral and cellular responses have been linked to clinical outcome (Yuan et al., 2011), or differentiation antigens (e.g. TYR, TYRP1, PMEL, and MLANA), were not differentially expressed (FIG. 14). Multiple genes involved in immune suppression enriched in ‘no benefit’ tumors, in particular another family of embryonically-restricted genes known as the pregnancy-specific glycoproteins (PSG1, PSG2, PSG4, PSG5, PSG6, PSG7, PSG8, PSG9, and PSG11; 7-48 fold). Secreted by the syncytiotrophoblasts of the placenta during pregnancy, the PSGs impair T cell proliferation and secrete the immunosuppressive cytokines IL-10 and TGF-B1, presumably to drive a locally immunosuppressive microenvironment required for fetal tolerance. Moreover, multiple subunits of the GABA A receptor, which has been implicated in mediating suppression of inflammatory macrophages and anti-tumor T cells, were also enriched in nonresponding tumors (GABRA3, GABRB1, GABRB2, GABRG2, GABRQ, and GABRR1; 2-108 fold). In contrast, no components of the GABA B receptor were similarly enriched, consistent with its lack of demonstrative immunosuppressive activity.

Other differentially expressed genes corresponding to anti-CTLA4 resistance included epithelial-to-mesenchymal transition (CLDN1, CLDN2, EYA1, SNAI1, TGFB2, WNT3), embryonic development/differentiation (HOXD13, HOXD11, HOXA2, HOXA5, HOXD10), angiogenesis (ANGPT1, ANG2, PDGFA), and extracellular matrix (PCDHB2, PCDHB3, PCDHB6, PCDHB10, PCDHGA3, PCDHGB1, PCDHGB2, EMILIN1, TNN). Genes listed in Table 2.

Next, another previously published clinical cohort consisting of chemotherapy-naïve responding (n=4) and resistant (n=2) pre-anti-CTLA4 melanomas (confirmation cohort) was queried (Snyder et al., 2014 The New England Journal of Medicine, 371(23):2189-99, incorporated herein by reference). Here too, CGA's from the Xq28 locus were upregulated in resistant tumors (FIG. 1B), confirming previous findings.

To further validate these results in a larger cohort, the transcriptomes of 473 metastatic melanomas from The Cancer Genome Atlas (TCGA) were analyzed, dividing them into “CGA-Xq28 high” and “CGA-Xq28 low” groups based on their expression of these 8 CGA's (Cancer Genome Atlas N. Genomic Classification of Cutaneous Melanoma. 2015 Cell, 161(7):1681-96, incorporated herein by reference). A statistically significant overlap was identified between genes co-enriched with the CTA-Xq28 locus in TCGA and genes enriched with nonresponding pre-anti-CTLA4 tumors (p<10⁻¹⁶) (TABLE 3, 4). As expected, no overlap was seen between “CGA-Xq28 high”-associated genes in TCGA and genes associated with responding tumors (p=1) (FIG. 1C).

Similarly, significant overlaps were identified between “CGA-Xq28 low”-associated genes in TCGA and genes associated with clinical benefit (p=1.6×10⁻⁵) but no overlaps with genes associated with “no benefit” tumors (p=1). Thus the enrichment of these 8 CTA's from the Xq28 locus in primary resistant melanomas to anti-CTLA4 therapy is consistently observed among three different cohorts.

The cohort was heavily pretreated with dacarbazine (DTIC) or temozolamide, two epigenetic modifiers. However, no effect of history of DTIC/temozolamide treatment on clinical outcome was identified (FIG. 9).

Because CGA expression is known to be regulated by DNA methylation (Sigalotti et al., 2002 Journal of immunotherapy, 25:16-26; Fratta et al., 2011 Molecular oncology, 5:164-82), locus specific methylation analysis was performed for the promoters of MAGEA3 and MAGEA6 as well as unique methylation sites within the gene bodies of MAGEA3, MAGEA6, and MAGE12. Within NB samples, significantly decreased DNA methylation was observed throughout the promoters for the MAGEA3 and MAGEA6 genes (FIG. 3A; n=3 CB vs n=3 NB, p=3×10⁻⁶) suggesting that methylation status of the Xq28-CGA locus is associated with clinical outcome to ipilimumab.

To further investigate DNA methylation patterns associated with CRMA expression, methylation data from TCGA melanoma samples was queried. Differential methylation analysis of 485,577 probes between samples with high and low expression of the CRMA locus (see STAR Methods for details) revealed 47 probes relatively hypermethylated in the “CRMA-high” group compared to 65,467 in the “CRMA-low” group (FIG. 3B). These 65,467 probes mapped across the genome, suggesting global hypomethylation in melanoma samples with high CRMA expression (FIG. 13B). Furthermore, methylation-specific PCR of MAGE-A2, MAGE-A3, and MAGE-A12 show decreased methylation in non-responding patients (FIG. 13A). Methylation status of the CRMA locus may therefore also be associated with clinical outcome to ipilimumab.

Example 2: Molecular Signatures of Response (Clinical Benefit)

Using a cutoff of 2-fold difference between the absolute medians of the two groups (nominal Mann-Whitney p<0.05), 175 protein-coding genes and 8 RNA genes co-enriched in the ‘clinical benefit’ tumors were identified. As the most upregulated gene, microRNA-211 (miR-211) was detected over 700-fold compared to ‘no benefit’ tumors (FIG. 1A, 4A). Housed within the melastatin gene (TRPM1, which was also upregulated over 30-fold), miR-211 has been recently discovered to account for the well-described tumor suppressive activity of melastatin by reducing melanoma invasive activity through effects on multiple processes including the TGF-beta signaling pathway. Indeed, among all 8 melastatin family members, only TRPM1 (FIG. 4A) was significantly enriched in ‘clinical benefit’ tumors. To evaluate whether miR-211 served a prognostic and/or a predictive role in the cohort, miR-211 levels were compared only between patients with a complete or partial response versus progressive disease. All patients with stable disease were removed from the analysis. Notably, it was observed that miR-211 levels remained significantly upregulated in the complete response/partial response group versus the progressive disease group, suggesting its ability to predict ipilimumab response in addition to prognosticating a more indolent clinical course. We also found miR-185 and miR-513a2 to be upregulated 24 and 31-fold respectively.

In contrast to the immunosuppressive nature of genes associated with primary resistance, an inflammatory, activated immunologic response was identified in the tumor microenvironment of ‘clinical benefit’ tumors, consistent with previous findings (FIG. 1B, 4B). Of 428 genes enriched in responding tumors, 174 (60%) were identified as immune-related. In contrast, in nonresponding tumors, only 17 of 975 (3%) protein-coding and RNA-associated genes were immune-related (FIG. 4B, 11C).

These immune-related genes were classified as involved in T cell infiltration (CD2, CD6, CXCL13), receptor signaling (CD3D, CD3E, CD3G, LCK, and T cell receptor alpha and beta genes [n=19]), activation (CD28, ICOS, EOMES, IL2RB, FASLG, SLAMF6), and cytotoxicity (GNLY, GZMA, GZMB, GZMH, GZMK, PRF1). Interestingly, an enrichment of immature T cells was noted from increased expression of the pre-T cell receptor alpha chain (PTCRA). Additionally, a striking number of immunoglobulin heavy and light chain genes (n=33) were upregulated in ‘clinical benefit’ tumors, thereby implicating humoral immunity (CD19, CD72, FCRL1/3, MS4A1). Dysfunction of a diverse immune infiltrate was suggested by enrichment of immune inhibitory receptors specific to or preferentially expressed by T cells (CTLA4, LAG3), B cells (CTLA4, FCRL1, FCRL3), macrophages (CD5L) and eosinophils/mast cells (SIGLEC8), depicting a paralyzed anti-tumor immune infiltrate. Also, upregulation of FAIM3/TOSO, the Fc receptor for IgM that is expressed on B and T cells, was observed. Recently, single cell transcriptomic studies implicated both FAIM3 and CD5L as key regulators of Th17 pathogenicity.

To validate the association of miR-211 with clinical benefit, TCGA melanoma transcriptomes were queried. It was identified that genes co-enriched with miR-211 significantly overlapped with genes enriched in clinically benefiting tumors (p=2.5×10⁻¹³) whereas no significant overlap was seen between genes co-enriched with miR-211 and genes enriched in resistant tumors (p=0.99) (FIG. 4C). Investigating the 22 genes that co-enriched with both response in the clinical cohort and miR-211 expression in TCGA, CD5L, IL12RB2, FAIM3, and PTCRA emerged, confirming the association of anti-CTLA4 response, miR-211 expression and diverse immune subpopulations. As described herein, miR-185 and miR-513A2 were significantly upregulated in clinically benefiting tumors (FIG. 4D). Furthermore, because all three miRs induce a proliferative melanoma phenotype while suppressing the invasive phenotype, the enrichment of proliferative and invasive gene signatures with clinical outcomes were investigated. It was identified that proliferative signatures significantly enrich in clinically benefiting tumors, while invasive signatures significantly enrich in no benefit tumors (FIG. 4E).

Example 3: Molecular Signatures of Clinical Outcome to CTLA4 Blockade are Unique and can Discriminate Response and Resistance

Although studies have suggested common genomic signatures of response (i.e. neoantigen load and clonality) for both CTLA4 and PD1 pathway blockade, the immunobiological processes driven by these two molecules are distinct. Thus, it was hypothesized that the transcriptional signatures of response and resistance to CTLA4 blockade would be unique and not shared with PD1 pathway antagonists. Recently, the genomic and transcriptomic features of response to anti-PD1 therapy in melanomas were reported (Hugo et al., 2016 Cell, 165(1):35-44, incorporated herein by reference). Expression of the Xq28 CTA's and miR-211 were interrogated in these cohorts; however, no correlation with clinical outcome (FIG. 5A-5C) was identified, confirming the hypothesis that the signatures of response and resistance to CTLA4 blockade are unique to anti-CTLA4 therapy and not shared with anti-PD1 therapy. Indeed, molecular signatures of innate resistance to PD1 blockade were also recently shown not to predict resistance to CTLA4 blockade. These results are consistent with the notion that the CTLA4 and PD1 pathways are biologically and clinically distinct.

To evaluate the ability of these gene expression signatures to accurately discriminate clinical outcome to CTLA4 blockade, the correlation of the greatest expression value from the Xq28 CGA cluster (comprising genes MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, GSAG2, and CAG3) was evaluated with expression of miR-211 for all 40 patients from Cohort 1, including the long-term survivors with no clinical benefit, thus examining a “real world” scenario (FIG. 6A). Also, a receiver-operator characteristic (ROC) analysis using the combined classifier of “Xq28+miR-211” was performed. The “Xq28+miR-211” classifier was created by combining expression of the maximally expressed gene in the Xq28 CGA cluster and miR-211 expression in a logistic regression model. Non-responders were characterized by high Xq28 CGA expression and low miR-211 expression. This “Xq28+miR-211” classifier more accurately discriminated patient outcomes than either neoantigen load or CTLA4 expression (FIG. 6B). In fact, AUCs of the latter two reached 0.68 while the new classifier achieved an AUC of 0.85. At 100% sensitivity, using neoantigen load or CTLA4 expression reached only 0% or 27% specificity whereas the new classifier achieved 40% specificity. A Kaplan-Meier analysis of post-ipilimumab overall survival demonstrated no significant effect of combining neoantigen load with CTLA4 gene expression (p=0.1) whereas the Xq28+miR-211 classifier significantly distinguished two clinical groups (p=0.005), especially in addition to both neoantigen load and CTLA4 expression (p=0.0003) (FIG. 6C). In summary, the expression analysis described herein uncovered transcriptomic determinants (i.e., biomarkers) of clinical outcome to CTLA4 blockade that outperform previously identified correlates and illuminate additional mechanisms of response and resistance.

Example 4: Cancer-Germline Antigens Discriminate Clinical Outcome to CTLA4 Blockade in a Validation Cohort and on the Protein Level

While the discovery cohort was generated from formalin-fixed samples from an observational, retrospective study, the findings were validated in an independent RNA-seq data set generated from cryopreserved tumors from a prospective, randomized trial using pre-treatment patient samples derived from the CheckMate 064 trial (Weber et al., 2016) (see STAR Methods for details). Again, the CRMA genes were amongst the most significantly upregulated genes (FIG. 2A-2B). Because overall survival data attributable to ipilimumab monotherapy was not available given the subsequent administration of nivolumab, the discovery cohort was re-classified based on response assessments used for the CheckMate 064 trial with “progressive disease (PD)” and “no PD” groups. RNA-seq expression values from the validation cohort were available for 5 of 8 genes in the CRMA locus (MAGEA3, MAGEA2, MAGEA2B, MAGEA12, and MAGEA6), and consistent and significant increases were observed in all of these genes in patients with PD in both discovery and validation cohorts (FIG. 2A-2B; 12B-C).

Because of prior reports of discordance between cancer-germline RNA and protein expression across cancers (Chen et al., 2014), immunohistochemistry (IHC) was performed on NB and CB samples using the MAGE-A antibody (clone 6C1), which is broadly reactive for gene products from the MAGE-A family recognizing MAGEA1, A2, A3, A4, A6, A10 and A12. IHC analysis demonstrated that the NB cohort comprised a significantly higher proportion of MAGE-A+ tumors compared to the CB cohort (FIG. 2C-2D, 73% vs 40%, p<0.05), consistent with the RNA-seq analysis. Thus, primary resistance to ipilimumab is strongly associated with baseline RNA and protein expression of a specific cluster of MAGE-A genes.

Detectable MAGE-A protein expression associated with inferior overall survival after ipilimumab therapy (FIG. 6D). In a multivariable analysis of these 40 patients that included evaluation of neoantigen load, CRMA expression emerged as the sole independent risk factor for poor outcome after ipilimumab therapy (Cox proportional-hazards model, p=0.018; FIG. 6E). Finally, CRMA expression did not discriminate overall survival in the untreated TCGA melanoma cohort, suggesting that the CRMA signature is potentially predictive for post-ipilimumab survival rather than prognostic for a clinically aggressive natural history (FIG. 6F). Taken together, these data suggest CRMA expression as a transcriptomic determinant of clinical outcome to CTLA4 blockade.

To control for potential artifacts from whole transcriptome RNA-seq (e.g. cDNA library synthesis, read alignment), results were confirmed by gene-specific RT-qPCR of the original tumor RNA in the discovery set using three different housekeeping genes (FIG. 7). To investigate potential mechanisms underlying the transcriptional enrichment of CRMA genes in resistant tumors, copy number variation and DNA methylation at this locus in the clinical trial samples was analyzed. No copy number alterations of this region based on analysis of matched whole-exome sequencing (WES) data were observed (FIG. 8). Neither gender nor prior exposure to cytotoxic therapy (i.e. dacarbazine/temozolomide) was associated with clinical outcome (FIG. 9; 10A). Using the ABSOLUTE algorithm (Carter et al., 2012), similar tumor purity estimates were identified in both patient groups, suggesting that relative enrichment of cancer cells in the NB group was unlikely to be an explanation for this finding (FIG. 10B).

Example 5: MAGE-A Proteins May Degrade the Danger Molecule HMGB1

Although MAGE proteins have often been studied as immunotherapeutic targets bound to HLA molecules on the cell surface (Van Der Bruggen et al., 2002), recent studies have attributed them with key oncogenic capacities. Expression of MAGE-A3/A6 is necessary for cancer cell viability and can be sufficient to transform cells (Pineda et al., 2015). Critical to the oncogenic functions of MAGEs may be their defining ability to bind to and potentiate the activity of various E3 ubiquitin ligases (Lee and Potts, 2017). MAGE-A2, MAGE-A3, and MAGE-A6 all share specific binding to the TRIM28 ubiquitin ligase. Multiple groups have demonstrated MAGE-TRIM28-induced ubiquitination and proteasomal degradation of the p53 tumor suppressor protein (Doyle et al., 2010) and more recently the AMPK complex which controls cellular metabolic pathways such as autophagy (Pineda et al., 2015).

As described herein, the MAGE-A genes within the CRMA locus may target proteins that are involved in immune priming (governed partly by the CTLA4 pathway) rather than immune effector function (governed partly by the PD1 pathway). The results of a screen for direct substrates of MAGE-A through in vitro ubiquitination reactions on protein microarrays containing >9000 recombinant proteins were previously reported (Pineda et al., 2015). As a significantly ubiquitinated target of the MAGE-TRIM28 complex, high-mobility group box 1 (HMGB1) emerged as a likely candidate for its well-described roles in both autophagy and immunogenic cell death that is required for dendritic cell-mediated priming of an adaptive immune response (Apetoh et al., 2007; Tang et al., 2010) (FIG. 11A). To investigate whether HMGB1 was a potential target of the MAGE-TRIM28 complex in melanoma tumors in vivo, immunofluorescence (IF) staining using both anti-HMGB1 and anti-MAGE-A antibodies (along with DAPI) was performed on tumor sections from 5 NB and CB tumors as well as a xenograft from the A375 human melanoma cell line (FIG. 11B). IF staining revealed the mutually exclusive expression of HMGB1 and MAGE-A proteins, with ubiquitous expression of HMGB1 protein in 3 of 3 MAGE-A negative/CB tumors and absent HMGB1 expression in 2 of 2 MAGE-A positive/NB tumors and the A375 human xenograft.

As a well-described damage-associated molecular pattern (DAMP), HMGB1 has been demonstrated to recruit a diverse inflammatory response by binding various toll-like receptors. In particular, HMGB1 can bind dsDNA to form immune complexes recognized by TLR9, resulting in secretion of immunostimulatory cytokines and proliferation of B cells (Avalos et al., 2010; Tian et al., 2007). Consistent with these studies, evidence for an inflammatory, activated immunologic response was identified in the tumor microenvironment of CB samples. Of 326 genes enriched in CB samples, 182 (55%) were identified as immune-related through manual curation, compared to only 16 of 457 (3.5%), in NB samples (Fisher's exact test, p<0.0001; FIG. 11C). In order to test the mutually exclusive expression of MAGE-A and HMGB1 proteins in melanoma, immunofluorescence staining was performed on a melanoma tissue microarray (TMA) comprising 100 samples (9 benign nevi tumors, 91 primary and metastatic melanomas) using antibodies against MAGE and HMGB1. The fraction of HMGB1 positive cells were comparable in MAGE negative cells from the benign nevi and malignant tumors, but was significantly reduced in cells from MAGE malignant samples ((26% and 31% vs 8%, Chi-square test p<2.2×10⁻¹⁶ FIG. 15A). Additionally, in 13 out of 15 melanomas that had any MAGE positive cells, at least 85% of MAGE+ cells lack HMGB1 (FIG. 15B). Supporting the finding that the MAGE-TRIM28 complex degrades HMGB1, significantly decreased expression of HMGB1 pathway genes (TLR9 and IL12A) was identified in no benefit tumors (FIG. 16).

Furthermore, to interrogate immune subpopulations, their involvement was computationally inferred using recently collated gene sets describing specific immune subsets (Angelova et al., 2015). Multiple B and T cell subpopulations were significantly enriched within CB transcriptomes comprising activated, immature and mature B cells along with central memory CD4+ T cells, effector memory CD8+ T cells, T helper 1 and 2 cells, gamma-delta T cells, and T regulatory cells (FIG. 11D). In addition, upregulation of genes related to T cell infiltration, T cell receptor signaling, humoral immunity and macrophage infiltration was also observed (Table 2). No immune subsets were significantly enriched in NB samples. Thus, the CRMA locus may contribute to ipilimumab resistance through targeted destruction of the DAMP, HMGB1, whose absence may restrain the initiation of an adaptive immune response.

Finally, to ascertain whether the MAGE-TRIM28 complex can suppress autophagy in melanoma, LC3B and p62 staining in MAGE-A stained melanomas was examined. Significantly reduced expression of the autophagy marker LC3B was identified in MAGE-A+ melanomas (FIG. 17A). Moreover, increased evidence of absent or impaired autophagy was found in 100% of MAGE-A positive melanomas (FIG. 17B).

Discussion

MAGE family members were first identified as targets of anti-tumor T cells in melanoma, and their restricted expression in immune-privileged gonadal tissues and various tumor types highlighted them as immunogenic targets (Coulie et al., 2014; De Plaen et al., 1994; Simpson et al., 2005; van der Bruggen et al., 1991). Therefore, the findings of a specific subcluster of MAGE-A genes overexpressed in melanomas resistant to CTLA4 blockade were unexpected. However, clinical efforts to immunotherapeutically target these proteins have yielded mixed results, suggesting their in vivo immunogenicity should not be assumed (Vansteenkiste et al., 2016). Indeed, many groups have demonstrated the association of CGAs and especially the MAGE family with poor prognostic features in melanoma such as ulceration, thickness, metastases and progression in contrast to the positive prognosis afforded by immune infiltration (Azimi et al., 2012; Barrow et al., 2006; Roeder et al., 2005).

One possible explanation for these results is that reduced Xq28-CGA expression in responding tumors is a manifestation of effective anti-MAGE-A immune activity. Responding melanoma samples are characterized by immune infiltrates that may have already selected against tumor cells expressing high levels of Xq28-CGA genes. However, it was observed that other melanoma antigens previously demonstrated to elicit cellular and humoral responses, such as NY-ESO-1 (another cancer-germline antigen) and various differentiation antigens, showed no evidence of selection in the analysis (FIG. 14). This particular MAGE-A subfamily has not been shown to provoke stronger immune responses than other cancer-germline or melanoma-associated antigens. As described herein, further investigation of in situ immune responses is pursued to rule out this possibility.

An alternative explanation is that these particular Xq28-CGA genes induce immune resistance. Recently described cell-intrinsic functions for MAGE-A3/A6 have implicated these proteins in oncogene addiction, the ubiquitination of key tumor suppressors—notably TP53 and AMPK—that contribute to oncogenesis, and the repression of autophagy (Doyle et al., 2010; Pineda et al., 2015). As described herein, degradation of a protein involved in immune priming (governed in part by the CTLA4 pathway) as opposed to immune effector function (mediated partly by the PD1 pathway) might explain the specificity of the Xq28-CGA cluster to CTLA4, but not PD1, blockade. In fact, an in vitro screen of ubiquitination targets of the MAGE-A3/6-TRIM28 E3 ubiquitin ligase revealed HMGB1, a damage-associated molecular pattern (DAMP) intimately involved in induction of cellular autophagy and immunogenic cell death (FIG. 11A-FIG. 11C) (Apetoh et al., 2007; Scaffidi et al., 2002; Tang et al., 2010; Yanai et al., 2009). Within responding tumor transcriptomes, upregulation of several B and T cell expression signatures were consistent with the immunostimulatory function of HMGB1 (Avalos et al., 2010; Ivanov et al., 2007; Li et al., 2013).

Binding of DAMPs to pattern recognition receptors (such as TLR family members) serve as ‘signal 0’ to kick-start the adaptive immune response through dendritic cell (DC) maturation and migration to the lymph nodes. There, DCs mediate antigen recognition by T cells (‘signal 1’), upregulate costimulatory receptors (‘signal 2’) and secrete polarization and differentiation cytokines (‘signal 3’) (Tang et al., 2012; Yatim et al., 2017). HMGB1 has been identified as a ‘signal 0’ that critically mediates immunogenic cell death—a process that has been proposed to rely on a combination of both antigenicity and adjuvanticity, the former conferred by neo-antigens (in tumors) and the latter provided by specific DAMPs (Galluzzi et al., 2017). Although melanomas have high neoantigen loads that correlate with response to checkpoint blockers, a defect in pathways required for cell death-associated release of DAMPs might decrease the adjuvanticity, and thus the overall immunogenicity, of a tumor. Importantly, both MAGE-A3/A6 and HMGB1 have been demonstrated to induce autophagy (Pineda et al., 2015; Tang et al., 2010), which is necessary for efficient dendritic cell cross-presentation of tumor antigens (Li et al., 2008). Indeed, short-hairpin RNA (shRNA)-mediated knockdown of HMGB1 or essential components of autophagy can abrogate immunogenic cell death (Apetoh et al., 2007; Michaud et al., 2011). Furthermore, loss-of-function polymorphisms in HMGB1-binding receptors or HMGB1 loss from malignant cells associate with poor outcome in patients treated with chemotherapeutic agents known to induce immunogenic cell death (Ladoire et al., 2015) and even in melanoma patients treated with DC-based vaccines (Tittarelli et al., 2012). Consequently, disabling the emission of danger signals such as HMGB1 may allow Xq28-CGA-expressing melanomas to inhibit the initiation of an adaptive immune response and impede the efficacy of CTLA4 blockade. Careful dissection of the role of MAGE-A-HMGB1 interactions in mediating outcome to CTLA4 blockade unveils new strategies to improve clinical responses to ipilimumab, for example through combination with HMGB1 receptor agonists.

Although the statistical stringency was relaxed because of the small discovery cohort, the finding of Xq28-CGA gene upregulation in primary resistance to CTLA4 blockade was validated through confirmation in a prospective, independent cohort and technical verification by qPCR and immunohistochemistry. Because both CTLA4 blockade and cancer vaccines impact immune priming and memory formation, the results presented herein may also explain the long history of unsuccessful cancer vaccination efforts targeting MAGEA3 and MAGEA6 (Palucka and Banchereau, 2014; Pedicord et al., 2011; Saiag et al., 2016; Vansteenkiste et al., 2016). The results presented herein also indicate that mechanisms of response and resistance to immune priming (e.g. CTLA4 blockade) may differ substantially from those relevant to clinical manipulation of effector immunity (e.g. PD1/PD-L1 blockade). As immunotherapeutic combinations are increasingly evaluated, understanding these mechanisms is important for precisely pairing patients with appropriate combinations to avoid toxicity and ensure efficacy. Nevertheless, these findings are investigated in larger, prospective cohorts to evaluate these signatures as potential biomarkers of outcome, and studied in preclinical models as potential therapeutic targets to sensitize to or combine with CTLA4 blockade.

STAR Methods

The following materials and methods were used in this example.

Study Design

A previously reported RNA-seq dataset of pre-therapy samples collected from a study cohort of 40 melanoma patients treated with ipilimumab (Van Allen et al., 2015) was analyzed. In this study, RNA and genomic DNA were extracted from formalin-fixed, paraffin-embedded (FFPE) tumor blocks, and Illumina's TruSeq Stranded Total RNA Sample Prep Kit was used to generate RNA-seq libraries. Patient classification was maintained from the original report (Table 1). The “clinical benefit” (CB) group (n=13) was defined as patients who achieved complete or partial response by RECIST criteria, or stable disease by RECIST criteria with overall survival greater than one year. The “no benefit” (NB) group (n=22) was defined as patients who had progressive disease by RECIST criteria or stable disease with overall survival less than 1 year. A third group of five patients was described with early progression on ipilimumab (progression-free survival <6 months) but overall survival exceeding 2 years. To identify genes associated with clinical benefit and no benefit, the differential expression analysis between the CB and NB groups was performed. The association of Xq28-CGA expression with survival outcome was evaluated in the entire cohort. Genes were identified as differentially expressed when their median expression differed by more than two-fold with a nominal one-sided p-value≤0.05 (Wilcoxon test).

An independent, validation cohort comprised 41 patients from the CheckMate 064 trial (Weber et al., 2016) treated with ipilimumab followed by nivolumab (Table 1). The trial also studied in parallel a cohort comprising patients treated with the reverse sequence of nivolumab followed by ipilimumab. Overall survival could not be assessed in this crossover design. Response assessments, collected at week 13 before the planned switch, were used to classify patients into either no progressive disease (“No PD”; comprising stable disease, complete response and partial response, n=12) or progressive disease (“PD”; n=29) from each arm. Tumor samples were cryopreserved in RNALater. RNA-seq libraries were generated using the Stranded TruSeq method, and 75 bp paired-end reads for duplexed samples were sequenced per lane (Expression Analysis, Inc; Morrisville, N.C.). RNA-Seq and associated clinical data were available for the following Xq28-CGA genes: MAGEA3, MAGEA2, MAGEA2B, MAGEA12, MAGEA6.

Xq28-CGA expression was evaluated in patients from two different anti-PD1-treated cohorts. Anti-PD1 cohort 1 comprised 28 pre-anti-PD1-treated tumors (Hugo et al., 2016); anti-PD1 cohort 2 comprised 37 pre-treatment tumors from the nivolumab followed by ipilimumab arm of the CheckMate064 trial (Hugo et al., 2016; Weber et al., 2016) (Table 1).

465 melanoma samples from TCGA (Cancer Genome Atlas, 2015) were used to further investigate identified gene expression and methylation signatures.

Processing and Analysis of Sequencing Data

RNA sequencing data from the discovery cohort was aligned to the reference human genome with STAR (Dobin et al., 2013), followed by removal of duplicates and quantification with RSEM (Li and Dewey, 2011). RNA sequencing data from the CheckMate064 trial was first aligned using STAR (Dobin et al., 2013) followed by removal of duplicate reads. Gene level quantification of the reads was performed with the htseq-count tool (Anders et al., 2015).

Whole exome data for 110 patients from the discovery cohort (including the 40 with transcriptomic data) (Van Allen et al., 2015) and Infinium 450K methylation chip data for 476 samples from TCGA (Cancer Genome Atlas, 2015) was also obtained.

Identification of Genes Associated with Xq28-CGA Expression in TCGA

A metagene was defined as one comprising the following Xq28-CGA genes: MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, and CSAG3 (MAGEA2B was not quantified by TCGA). The expression of this metagene was defined as the geometric mean of its components and was computed for each of 465 TCGA melanoma samples. TCGA samples with expression values in the bottom and top quartiles for this metagene were classified into “Xq28-CGA-low” (n=117) and “Xq28-CGA-high” (n=116) groups respectively. An unbiased gene expression analysis between these two groups was performed using one-sided Wilcoxon tests with a false discovery rate (FDR) threshold of 0.05 and two-fold change threshold.

Validation of Genes by Quantitative Polymerase Chain Reaction

Expression of target genes in the discovery cohort (Van Allen et al., 2015) from RNA that was extracted for RNA-sequencing was validated. TaqMan gene expression assays (Applied Biosystems, Foster City, Calif.) was used and cDNA amplification was performed using the TaqMan Gene Expression Master Mix (Applied Biosystems) on an Applied Biosystems 7500HT Fast real-time polymerase chain reaction (PCR) System (10-minute enzyme activation and 40 cycles of 15 s at 95° C., 1 minute at 60° C.). Samples were measured in duplicate; “undetermined” values were assigned a cycle threshold (Ct) of 40. HPRT1, GAPDH, and PGK1 were used as housekeeping genes to calculate relative expression values according to the delta-Ct method.

Identification of Differentially Methylated Probes Between Xq28-CGA-Low and -High Groups in TCGA

Level3 Infinium 450K methylation chip data was retrieved from TCGA for “Xq28-CGA-low” (n=117) and “Xq28-CGA-high” (n=116) groups. A probe-level comparison was performed between the two groups using Wilcoxon tests with an FDR of 0.05 for all 485,577 CpG probes. A probe with higher median beta values in one group was considered relatively hypermethylated in that group compared to the other.

Copy Number Analysis

The clinical benefit (CB) and no benefit (NB) groups were tested for variations in germline and somatic CNVs in Xq28 locus using GATK 4 target coverage denoising and ACNV pipelines. Raw coverage on whole exome Agilent targets for 110 normal and tumor samples was collected and GC bias was corrected for. The 40 samples with RNA-seq data used in this study were set aside and the remaining 70 samples were used to learn the target coverage bias profile (“panel of normals”). Then, the coverage profile of samples used in this study were denoised and normalized using the obtained panel of normals. Tumor samples with anomalously low signal-to-noise ratio and normal samples with significant contamination were detected and excluded from the analysis. Empirical distributions of raw copy ratios on all 16 Agilent targets in the Xq28 locus were calculated using an agnostic prior distribution and copy ratio likelihoods for each sample. Absolute copy ratios with respect to diploid were estimated by performing allelic CNV analysis, detecting copy neutral autosomal intervals, and normalizing the raw copy ratios accordingly.

The two groups were tested for germline and somatic copy number variations in the Xq28 locus using the two-sample KS test. The test was performed separately for each target, and for the copy ratio average on all 16 targets in the Xq28 locus. The copy ratio distributions in each case were identified via empirical bootstrap.

Amplicon Methylation Analysis

Genomic DNA samples of male patients was bisulfite-treated (EZ DNA Methylation-Gold™ Kit, Zymo Research) and individual amplicons were amplified via PCR (using TaKaRa EpiTaq™ HS, Clonetech). The following primer pairs were used: MAGEA3, MAGEA6 and MAGEA12 gene body, Forward Primer: GATTGTGTTTTTGAGGAGAAAATTT (SEQ ID NO: 206), Reverse Primer: CTCCCACTAACCCTAACTACAACTC (SEQ ID NO: 207). MAGEA3 and MAGEA6 gene promoter, Forward Primer: AATTTTAGGATTTTGAGGGATGAT (SEQ ID NO: 208), Reverse Primer: AAACCCTCTATCTAAAATAAAACCC (SEQ ID NO: 209). PCR products were subcloned (One Shot® TOP10 Chemically Competent E. coli, NEB) and individual colonies were sequenced for subsequent methylation analysis. For the local regression analysis (R package ‘msir’) the span smoothing parameter for loess was set to 0.4.

Immunohistochemistry (IHC) and Immunofluorescence (IF)

All specimens were evaluated by conventional histopathology. Antibodies used for IHC and IF included mouse anti-MAGE antibody (6C1; Santa Cruz Biotechnology, San Diego, Calif. USA) and rabbit anti-HMGB1 antibody (ab18256; Abcam, Cambridge, Mass.). Immunohistochemistry was performed with pressure cooker heat-induced epitope retrieval on 4-mm-thick sections prepared from formalin-fixed, paraffin-embedded tissues. In addition to detection of biomarker antibodies by use of chromogen vector NovaRed peroxidase substrate (Vector laboratory, Burlingame, Calif., USA), selected samples were evaluated by a dual labeling approach by combining NovaRed with a blue chromogen vector Blue AP substrate (Vector laboratory). Positive and negative tissue controls and isotype-specific irrelevant antibody controls were used to ensure specificity. Consistent with other reports of IHC for MAGE-A protein, nuclear and/or cytoplasmic staining was interpreted as a positive staining pattern; staining in any cancer cells, irrespective of percentage of positive cells or intensity, was regarded as positive.

Dual-labeling immunoflourescence was performed to complement immunohistochemistry as a means of two-channel identification of epitopes co-expressed in similar or overlapping sub-cellular locations. Briefly, 4-mm-thick paraffin sections were incubated with 1:100 mouse anti-MAGE antibody+1:1000 rabbit anti-HMGB1 antibody at 4° C. overnight and then incubated with 1:2000 Alexa Fluor 594-conjugated anti-mouse IgG and Alexa Fluor 488-conjugated anti-rabbit IgG (Invitrogen) at room temperature for 1 hour. The sections were cover slipped with ProLong Gold anti-fade with DAPI (Invitrogen). Sections were analyzed with a BX51/BX52 microscope (Olympus America, Melville, N.Y., USA), and images were captured using the CytoVision 3.6 software (Applied Imaging, San Jose, Calif., USA). Single label immunofluorescence was also performed using isotype-specific irrelevant primary antibodies and with switching of the secondary antibodies to ensure specificity and exclude cross reactivity.

Survival Analysis

The association of Xq28-CGA expression with overall survival was evaluated using the Kaplan-Meier method. In the discovery cohort, patients with Xq28-CGA expression values above the median were considered “high” and below the median were considered “low.” The effect of Xq28-CGA expression on overall survival adjusting for age, gender, number of pre-therapies, M-stage, LDH and neoantigen load was assessed using the Cox proportional hazards model.

Statistical Analysis

Differential expression and methylation analyses within TCGA samples were performed using a false discovery rate (Benjamini-Hochberg) of 0.05. Hypergeometric tests were used to evaluate overlap of differentially expressed genes between the clinical and TCGA cohorts. Multivariable survival analysis was performed using the Cox proportional hazards model (R package ‘coxph’). All statistical analyses were done using R version-3.2.5. Overlaps of gene lists with pathways in the PANTHER (Protein ANalysis THrough Evolutionary Relationships) database (containing 177 pathways) were evaluated with the overrepresentation test using the Bonferroni correction (Mi et al., 2016).

TABLE 1 Clinical characteristics of discovery and validation cohorts Time to Overall progression survival # prior ID Gender Age RECIST (wks) (yrs) LDH M class therapies Discovery Cohort Pat02 female 42 SD 77 4.5 1 M1c 1 (Van Allen et al): Pat04 male 71 PR 92 2.7 0 M1b 7 Clinical benefit (CB) Pat29 male 82 X 49 3.6 0 M1c 1 Pat38 male 45 PR 43 4.2 0 M1c 2 Pat39 male 67 CR 212 4.1 0 M1b 1 Pat47 male 78 CR 158 3 0 M1c 1 Pat49 male 36 SD 23 2.8 0 M1c 0 Pat79 male 69 PR 58 2.2 0 M1b 1 Pat80 male 48 SD 26 2 1 M1c 1 Pat88 female 60 SD 95 2.7 NA M1c 0 Pat90 male 59 PR 96 2.8 0 M1c 1 Pat123 female 50 SD 78 2.3 1 M1c 5 Pat126 male 77 PR 27 1.8 1 M1b 1 Discovery Cohort Pat03 female 61 PD 11 0.3 1 M1c 3 (Van Allen et al): Pat06 male 33 PD 11 0.4 0 M1c 4 No benefit (NB) Pat08 male 73 PD 10 0.4 0 M1c 2 Pat118 female 48 PD 12 0.4 0 M1c 3 Pat14 male 32 PD 4 0.1 1 M1c 4 Pat15 male 59 PD 3 0.5 0 M1c 0 Pat19 male 78 PD 10 0.3 0 M1c 1 Pat25 male 69 PD 10 0.9 1 M1c 1 Pat33 male 65 PD 30 0.6 1 M1c 3 Pat36 female 52 PD 6 0.1 1 M1c 3 Pat37 female 47 PD 3 0.2 1 M1c 1 Pat40 male 74 PD 5 0.1 1 M1c 3 Pat41 male 64 PD 8 0.4 1 M1c 1 Pat43 female 75 PD 5 0.1 1 M1b 2 Pat44 female 57 PD 9 0.7 1 M1c 1 Pat45 male 68 PD 9 0.2 1 M1c 1 Pat46 female 36 PD 5 0.4 0 M1b 1 Pat50 male 77 PD 9 0.2 0 M1c 0 Pat81 female 54 PD 11 1.7 0 M1a 0 Pat85 male 83 PD 12 1.3 0 M1c 1 Pat86 male 55 SD 22 0.8 0 M1a 0 Pat98 female 57 PD 11 0.4 0 M1c 0 Discovery Cohort Pat119 female 68 PD 12 2.2 0 M1b 1 (Van Allen et al): pat16 male 61 PD 20 3.8 0 M1c 1 Long-term survival Pat27 male 77 PD 11 3.2 1 M1c 2 with no clinical Pat28 male 22 PD 15 2.8 0 M1c 0 benefit Pat83 male 61 PD 15 2.2 1 M0 1 ID Gender Age RECIST Validation cohort 1 Male 47 SD (Weber et al)Ipilimumab 2 Male 82 PR --> nivolumab: No 3 Male 31 PR progressive disease 4 Male 70 SD 5 Female 48 SD 6 Male 66 SD 7 Male 66 PR 8 Male 51 SD 9 Male 74 SD 10 Male 67 PR 11 Male 54 SD 12 Male 63 SD Validation cohort 13 Male 84 PD (Weber et al)Ipilimumab 14 Male 37 PD --> nivolumab: 15 Male 46 PD Progressive disease 16 Female 64 PD 17 Male 73 PD 18 Male 74 PD 19 Male 56 PD 20 Male 78 PD 21 Female 62 PD 22 Female 55 PD 23 Female 75 PD 24 Female 44 PD 25 Female 63 PD 26 Male 38 PD 27 Male 53 PD 28 Male 36 PD 29 Female 35 PD 30 Male 55 PD 31 Male 74 PD 32 Female 78 PD 33 Male 79 PD 34 Male 84 PD 35 Male 66 PD 36 Female 56 PD 37 Male 64 PD 38 Female 63 PD 39 Female 73 PD 40 Male 52 PD 41 Male 75 PD Validation cohort 34 Male 65 PR (Weber et al) Nivolumab 35 Female 27 PR --> ipilimumab: No 36 Female 42 PR progressive disease 37 Male 74 PR 38 Male 58 SD 39 Male 57 SD 40 Female 64 PR 41 Female 40 SD 42 Male 62 PR 43 Male 63 PR 44 Male 36 SD 45 Male 46 SD 46 Male 73 SD 47 Male 57 SD 48 Male 60 PR 49 Male 52 SD 50 Female 58 SD 51 Female 47 PR 52 Female 59 PR 53 Male 89 SD 54 Male 72 PR 55 Male 56 PR 56 Male 81 PR Validation cohort 57 Male 62 PD (Weber et al)Nivolumab 58 Female 62 PD --> ipilimumab: 59 Female 72 PD Progressive disease 60 Male 73 PD 61 Female 49 PD 62 Male 40 PD 63 Male 71 PD 64 Female 32 PD 65 Male 36 PD 66 Male 60 PD 67 Male 70 PD 68 Male 30 PD 69 Male 52 PD 70 Male 77 PD

TABLE 2 Genes enriched in No Benefit and Clinical Benefit group Gene Gene Nome Fold Change P-value Group MAGEA2 melanoma antigen family A, 2 194.87 0.001681771 NB AC093787.1 191.37 0.014074651 NB KRT8P8 keratin 8 pseudogene 8 115.36 0.000437919 NB CSAG4 CSAG family, member 4 (pseudogene) 113.21 0.001374253 NB GABRA3 gamma-aminobutyric add (GABA) A receptor, alpha 3 110.18 0.00105356 NB MAGEA2B melanoma antigen family A, 2B 102.86 0.001902564 NB CSAG2 CSAG family, member 2 95.83 0.000939032 NB MKRN9P makorin ring finger protein 9, pseudogene 93.52 0.001122703 NB MAGEA6 melanoma antigen family A, 6 87.63 0.005477973 NB CSAG3 CSAG family, member 3 87.39 0.001254778 NB RP1-273G13.1 84.57 0.001749305 NB EYA1 eyes absent homolog 1 (Drosophila) 79.9 0.003059735 NB MIR218-1 microRNA 218-1 77.65 0.004961686 NB CSAG1 chondrosarcoma associated gene 1 73.33 0.008425839 NB RP11-379D21.3 67.64 0.003911124 NB MAGEA12 melanoma antigen family A, 12 67.35 0.013100955 NB MAGEA3 melanoma antigen family A, 3 58.31 0.008391308 NB RP11-360D2.1 55.78 0.004483201 NB MIR1262 micraRNA 1262 48.86 0.004516422 NB PSG6 pregnancy specific beta-1-glycoprotein 6 47.93 0.009417526 NB PSG11 pregnancy specific beta-1-glycoprotein 11 42.47 0.001216848 NB RP1-13D10.2 40.78 0.002072617 NB OR11H12 olfactory receptor, family 11, subfamily H, member 12 39.49 0.004790916 NB MAGEC1 melanoma antigen family C, 1 37.21 0.024814077 NB CTD-2302A16.2 36.28 0.038385003 NB CTD-2201G16.1 36.19 0.025889607 NB RP11-526L8.1 34.16 0.026158447 NB RP11-804F13.2 34.02 0.001073914 NB PSG8 pregnancy specific beta-1-glycoprotein 8 31.38 0.02875596 NB SOX5P SRY (sex determining region Y)-box 5 pseudogene 27.52 0.010553127 NB AC097635.5 27.14 0.013029879 NB SLC25A15P4 solute carrier family 25 (mitochondrial carrier; ornithin 

26.67 0.033214335 NB RP11-533K9.3 25.7 0.025889607 NB NFYAP1 nuclear transcription factor Y, alpha pseudogene 1 25.61 0.007926133 NB GJB6 gap junction protein, beta 6, 30 kDa 25.6 0.002430921 NB GABRQ gamma-aminobutyric acid (GABA) A receptor, theta 25.08 0.000665219 NB XIST X inactive specific transcript (non-protein coding) 24.53 0.015742933 NB TNP1 transition protein 1 (during histone to protamine repla 

23.74 0.030404894 NB AC135995.2 23.56 0.015640563 NB SNORA27 small nucleolar RNA, H/ACA box 27 22.87 0.014772695 NB SERPINA5 serpin peptidase inhibitor, clade A (alpha-1 antiprotein 

22.55 0.001957165 NB RP11-250B2.2 21.76 0.003178944 NB CTC-329D1.2 21.66 0.010553127 NB MAGEA1 melanoma antigen family A, 1 (directs expression of an 

21.42 0.016995145 NB RP11-379D21.2 20.89 0.001703467 NB OR2M3 olfactory receptor, family 2, subfamily M, member 3 20.48 0.00982579 NB AGMO alkylglycerol monooxygenase 20.21 0.001148356 NB RP11-728C8.1 20.06 0.008215814 NB CYP26A1 cytochrome P450, family 26, subfamily A, polypeptide 

19.61 0.008358255 NB RP11-685G9.2 19.57 0.003476545 NB RP1-221C16.7 19.51 0.012379028 NB ENSAP1 endosulfine alpha pseudogene 1 19.32 0.042437855 NB PSG5 pregnancy specific beta-1-glycoprotein 5 19.2 0.009622364 NB AC007312.3 19.11 0.038857039 NB LA16c-4G1.5 19.11 0.004269868 NB RP11-114H24.7 19.09 0.039174691 NB PSG2 pregnancy specific beta-1-glycoprotein 2 19.08 0.014252125 NB AC126339.2 18.9 0.044112433 NB RP4-535B20.1 18.85 0.049098599 NB RP11-290F24.3 18.84 0.002622662 NB PPM1AP1 protein phosphatase, Mg2+/Mn2+dependent 1A, pseu 

18.79 0.020779381 NB HMGN1P17 high mobility group nucleosome binding domain 1 pse 

18.67 0.023187328 NB PSG10P pregnancy specific beta-1-glycoprotein 10, pseudogene 18.44 0.011708098 NB OR7E156P olfactory receptor, family 7, subfamily E, member 156 

18.38 0.023557449 NB RP4-610C12.3 18.33 0.004753871 NB FPGT-TNNI3K FPGT-TNNI3K readthrough 18.05 0.008875911 NB RP4-710M3.1 17.9 0.030948543 NB AC010724.2 17.64 0.038448428 NB RP11-17A1.2 17.54 0.002310348 NB VENTXP5 VENT homeobox pseudogene 5 17.49 0.000887029 NB CFHR4 complement factor H-related 4 17.16 0.00659527 NB CCDC42 coiled-coil domain containing 42 16.99 0.01123551 NB RP1-232L24.2 16.31 0.024728355 NB IL13RA2 interleukin 13 receptor, alpha 2 16.3 0.031216315 NB OR11H12 olfactory receptor, family 11, subfamiy H, member 12 16.28 0.000660549 NB RP11-9H16.1 16.25 0.021446576 NB RP11-670N15.2 16.22 0.032630531 NB RP11-326E22.1 16.08 0.006136197 NB ASS1P9 argininosuccinate synthetase 1 pseudogene 9 15.74 0.009002927 NB RP11-310H4.5 15.28 0.00216299 NB NXT1P1 NTF2-like export factor 1 pseudogene 1 15.26 0.042179156 NB HMGN2P25 high mobility group nucleosomal binding domain 2 pse 

15 0.045821322 NB MAGEC2 melanoma antigen family C, 2 14.91 0.024662434 NB RPS12P21 ribosomal protein S12 pseudogene 21 14.9 0.038857039 NB HSPB3 heat shock 27 kDa protein 3 14.68 0.011561372 NB HOXD11 homeobox D11 14.62 0.002516383 NB ANKRD7 ankyrin repeat domain 7 14.38 0.007839036 NB PSG1 pregnancy specific beta-1-glycoprotein 1 14.26 0.014251282 NB GDNF glial cell derived neurotrophic factor 14.13 0.00731008 NB RP3-406A7.5 14.13 0.047995343 NB PSG7 pregnancy specific beta-1-glycoprotein 7 (gene/pseudo 

14.09 0.025544289 NB RP3-432I18.1 13.99 0.042179156 NB GAGE12D G antigen 12D 13.96 0.020177433 NB RPL7P56 ribosomal protein L7 pseudogene 56 13.44 0.006122033 NB GTF2A1L general transcription factor IIA, 1-like 13.36 0.039174691 NB FBP2 fructose-1,6-bisphosphatase 2 13.18 0.040365068 NB ACTBP8 actin, beta pseudogene 8 13.05 0.006307706 NB MAGEA11 melanoma antigen family A, 11 13.03 0.018744092 NB RSL24D1P2 ribosomal L24 domain containing 1 pseudogene 2 13 0.035978626 NB OR2H5P olfactory receptor, family 2, subfamily H, member 5 ps 

12.88 0.029540253 NB AC002076.9 12.77 0.024189646 NB C1QTNF9-AS1 C1QTNF9 antisense RNA 1 12.72 0.011759771 NB OR52N2 olfactory receptor, family 52, subfamily N, member 2 12.7 0.010901498 NB RP11-973N13.3 12.53 0.002704784 NB ANKRD45 ankyrin repeat domain 45 12.49 0.008813638 NB OR2T12 olfactory receptor, family 2, subfamily T, member 12 12.45 0.048632504 NB PSG4 pregnancy specific beta-1-glycoprotein 4 12.22 0.003256582 NB SPANXB2 SPANX family, member B1 12.08 0.015009075 NB CTD-2206G10.1 11.79 0.020435079 NB CHL1-AS2 CHL1 antisense RNA 2 11.76 0.008620126 NB RP11-316E14.2 11.63 0.042283368 NB PLAC1 placenta-specific 1 11.62 0.032391329 NB MRPS17P9 mitochondrial ribosomal protein S17 pseudogene 9 11.55 0.042179156 NB RP11-290F24.4 7.84 0.025644286 NB AL359392.1 7.83 0.047209651 NB BAI3 7.82 0.008070194 NB ZEB2P1 zinc finger E-box binding homeobox 2 pseudogene 1 7.78 0.010062094 NB CDK2AP2P1 cycin-dependent kinase 2 associated protein 2 pseudo 

7.74 0.048733769 NB AC105461.1 7.72 0.049369302 NB RP11-138J23.1 7.7 0.034551581 NB RP11-132G10.2 7.68 0.034369721 NB SLC9C2 solute carrier family 9, member C2 (putative) 7.59 0.001888785 NB NELL1 NEL-like 1 (chicken) 7.59 0.028688235 NB RPS18P1 ribosomal protein S18 pseudogene 1 7.59 0.04941826 NB RP11-1007G5.2 7.49 0.041920281 NB OR9A3P olfactory receptor, family 9, subfamily A, member 3 ps 

7.42 0.0131522 NB SLCO1A2 solute carrier organic anion transporter family, membe 

7.28 0.038479039 NB GRIA2 glutamate receptor, ionotropic, AMPA 2 7.27 0.029382731 NB METTL11B methyltransferase like 11B 7.19 0.042437855 NB MYLKP1 myosin light chain kinase pseudogene 1 7.19 0.041397125 NB LINC00189 long intergenic non-protein coding RNA 189 7.1 0.035553997 NB RP11-384F7.2 7.07 0.017952081 NB MAGEA9B melanoma antigen family A, 9B 7.06 0.014094423 NB SRGAP3-AS1 SRGAP3 antisense RNA 1 7.05 0.046077602 NB PSG9 pregnancy specific beta-1-glycoprotein 9 7.05 0.030297821 NB RP11-959F10.4 7.04 0.001238714 NB OR52E8 olfactory receptor, family 52, subfamily E, member 8 6.97 0.042179156 NB RP11-1365D11.1 6.93 0.041659897 NB AC018682.6 6.92 0.018687432 NB HNRNPCL1 heterogeneous nuclear ribonucleoprotein C-like 1 6.89 0.002516383 NB NLRP4 NLR family, pyrin domain containing 4 6.84 0.010808151 NB LGALS12 lectin, galactoside-binding, soluble, 12 6.78 0.037825665 NB DCAF4L2 DDB1 and CUL4 associated factor 4-like 2 6.74 0.032737245 NB OR5K1 olfactory receptor, family 5, subfamily K, member 1 6.67 0.007926133 NB AC079753.5 6.63 0.048733769 NB TPTE2P6 transmembrane phosphoinositide 3-phosphatase and t 

6.62 0.003242319 NB LGI4 leucine-rich repeat LGI family, member 4 6.57 0.005926234 NB KANK4 KN motif and ankyrin repeat domains 4 6.55 0.041739925 NB TDPX2 6.49 0.01692508 NB FPGT-TNNI3K FPGT-TNNI3K readthrough 6.48 0.001351513 NB RP11-206P5.2 6.46 0.036254638 NB PI15 peptidase inhibitor 15 6.46 0.011925792 NB LGI1 leucine-rich, glioma inactivated 1 6.45 0.021949515 NB OPRD1 opioid receptor, delta 1 6.42 0.044163971 NB TAAR6 trace amine associated receptor 6 6.42 0.006632488 NB ISL2 ISL LIM homeobox 2 6.42 0.009764943 NB OR7E91P olfactory receptor, family 7, subfamily E, member 91 ps 

6.41 0.036277389 NB ANKFN1 ankyrin-repeat and fibronectin type III domain containi 

6.41 0.006344984 NB UROC1 urocanate hydratase 1 6.38 0.011561372 NB IGFN1 immunoglobulin-like and fibronectin type III domain co 

6.36 0.042370292 NB PRL prolactin 6.3 0.03495366 NB FRAS1 Fraser syndrome 1 6.22 0.000149689 NB FSCN1 fascin actin-bundling protein 1 6.21 0.000438786 NB FEM1AP4 fem-1 homolog a (C. elegans) pseudogene 4 6.21 0.007806012 NB TERF1P1 telomeric repeat binding factor (NIMA-interacting) 1 ps 

  6.21 0.043875977 NB RP11-54D18.2 6.2 0.023106635 NB PCDHB3 protocadherin beta 3 6.12 0.002421425 NB TOB2P1 transducer of ERBB2, 2 pseudogene 1 6.06 0.024375591 NB OTOGL otogelin-like 6.06 0.018812935 NB C1orf185 6.05 0.012843104 NB SYTL5 synaptotagmin-like 5 11.47 0.014391143 NB RPS2P39 ribosomal protein S2 pseudogene 39 11.44 0.025105736 NB CEACAMP5 carcinoembryonic antigen-related cell adhesion molec 

11.43 0.005369816 NB TFF2 trefoil factor 2 11.43 0.008928345 NB AC016737.1 11.35 0.007926133 NB RP11-438N16.2 11.34 0.016120921 NB RP11-634B7.5 11.31 0.038385003 NB RP11-108F13.2 11.3 0.00239315 NB RP11-386I14.3 11.25 0.015009075 NB RP11-885B4.1 11.24 0.019586567 NB GRIN2B glutamate receptor, ionotropic, N-methylD-aspartate 

  11.08 0.000583885 NB RPSAP43 ribosomal protein SA pseudogene 43 11.05 0.04941826 NB OR2M2 olfactory receptor, family 2, subfamily M, member 2 11.04 0.017682347 NB RP11-69I13.1 10.87 0.011874924 NB RPS20P24 ribosomal protein S20 pseudogene 24 10.66 0.025280278 NB CASP12 caspase 12 (gene/pseudogene) 10.62 0.00105356 NB AKAP6 A kinase (PRKA) anchor protein 6 10.55 0.004785714 NB RP11-294J22.6 10.54 0.049758592 NB RP1-273G13.2 10.4 0.001483816 NB RP11-115C10.1 10.28 0.014679168 NB OR2J3 olfactory receptor, family 2, subfamily J, member 3 10.2 0.04941826 NB OR11H1 olfactory receptor, family 11, subfamily H, member 1 10.15 0.014094423 NB OBP2A odorant binding protein 2A 10.14 0.038385003 NB GAGE13 G antigen 13 10.07 0.048733769 NB SPINK13 serine peptidase inhibitor, Kazal type 13 (putative) 10 0.000900029 NB RP11-972K6.1 10 0.046077602 NB KRT18P29 keratin 18 pseudogene 29 9.86 0.001205418 NB RAET1L retinoic acid early transcript 1L 9.74 0.028546721 NB MYH1 myosin, heavy chain 1, skeletal muscle, adult 9.7 0.001681771 NB RP11-36B15.1 9.49 0.047995343 NB RP11-889L3.4 9.46 0.025105736 NB GLRA4 glycine receptor, alpha 4 9.39 0.00250769 NB RP11-7G23.5 9.37 0.041659897 NB AC008537.1 9.36 0.00140516 NB AP002380.1 9.3 0.009891102 NB RP3-461F17.2 9.26 0.04756409 NB CR848007.6 9.19 0.036211389 NB MYLK-AS1 MYLK antisense RNA 1 9.17 0.029945212 NB MAGEB2 melanoma antigen family B, 2 9.09 0.015914763 NB CFL1P2 cofilin 1 (non-muscle) pseudogene 2 9.04 0.010626103 NB AC007557.1 9.03 0.011581165 NB OR1D4 olfactory receptor, family 1, subfamily D, member 4 (ge 

8.93 0.017845056 NB MAGEC3 melanoma antigen family C, 3 8.81 0.001071925 NB AC087491.2 8.73 0.049369302 NB TTLL10-AS1 TTLL10 antisense RNA 1 8.6 0.038385003 NB RP11-416N13.1 8.46 0.04756409 NB AADAC arylacetamide deacetylase 8.36 0.028010999 NB RPL27AP8 ribosomal protein L27a pseudogene 8 8.28 0.003936897 NB OR2M5 olfactory receptor, family 2, subfamily M, member 5 8.21 0.019371037 NB FAM3D family with sequence similarity 3, member D 8.17 0.043875977 NB SLCO1B1 solute carrier organic anion transporter family, membe 

  8.15 0.045588672 NB AC093110.3 8.09 0.006633885 NB FUCA1P1 fucosidase, alpha-L-1, tissue pseudogene 1 8.05 0.004515513 NB MAGEA8 melanoma antigen family A, 8 8.05 0.029382731 NB RP11-557F20.2 8 0.029762656 NB CIB4 calcium and integrin binding family member 4 7.96 0.013029879 NB SFRP1 secreted frizzled-related protein 1 7.93 0.018812935 NB RP11-315I20.3 6.02 0.022360081 NB TRIM71 tripartite motif containing 71, E3 ubiquitin protein ligas 

5.97 0.045176166 NB CRB1 crumbs family member 1, photoreceptor morphogenes 

5.95 0.004290131 NB HPSE2 heparanase 2 5.92 0.031391184 NB FSHR follide stimulating hormone receptor 5.86 0.020177433 NB RND2 Rho family GTPase 2 5.86 0.003059735 NB VSX1 visual system homeobox 1 5.86 0.003695654 NB GJB2 gap junction protein, beta 2, 26 kDa 5.85 0.001681771 NB LEFTY2 left-right determination factor 2 5.8 0.030404894 NB PPP1R1C protein phosphatase 1, regulatory (inhibitor) subunit 1 

5.8 0.000704181 NB ELOVL2 ELOVL fatty acid elongase 2 5.74 0.02643572 NB AC107983.2 5.71 0.008917729 NB RP13-210D15.1 5.71 0.042179156 NB MPZ myelin protein zero 5.67 0.033656613 NB DNM3OS DNM3 opposite strand/antisense RNA 5.66 0.028426013 NB KLHL13 kelch-like family member 13 5.65 0.031092971 NB HHATL hedgehog acyltransferase-like 5.64 0.0186415 NB RP11-351M16.1 5.63 0.046077602 NB HCN1 hyperpolarization activated cyclic nucleotide-gated pot 

  5.61 0.021040385 NB CEACAMP1 carcinoembryonic antigen-related cell adhesion molec 

5.61 0.036277389 NB RP11-536C10.24 5.59 0.006136197 NB CITED4 Cbp/p300-interacting transactivator, with Glu/Asp-rich 5.58 0.007203049 NB AMDP1 5.55 0.045085282 NB RP13-547K6.1 5.53 0.010808151 NB C5orf27 5.49 0.033515231 NB SLC22A10 solute carrier family 22, member 10 5.42 0.008187016 NB TSPEAR thrombospondin-type laminin G domain and EAR repea 

5.42 0.007254752 NB U82695.9 5.42 0.001227747 NB KIAA0087 KIAA0087 5.4 0.000569695 NB MOCS1P1 molybdenum cofactor synthesis 1 pseudogene 1 5.37 0.012166712 NB MYH2 myosin, heavy chain 2, skeletal muscle, adult 5.37 0.005926234 NB RP11-959F10.5 5.36 0.00328693 NB SERPINA4 serpin peptidase inhibitor, clade A (alpha-1 antiprotein 

5.3 0.006480309 NB TPD52L1 tumor protein D52-like 1 5.28 0.028688235 NB SLC30A8 solute carrier family 30 (zinc transporter), member 8 5.27 0.034885381 NB RGS6 regulator of G-protein signaling 6 5.25 0.016310813 NB DLX6-AS2 DLX6 antisense RNA 2 5.24 0.045588672 NB C9orf153 5.24 0.009764943 NB MYH13 myosin, heavy chain 13, sleletal muscle 5.24 0.002724323 NB CA10 carbonic anhydrase X 5.24 0.006122033 NB DGKB diacylglycerol kinase, beta 90 kDa 5.23 0.012651023 NB GABRB1 gamma-aminobutyric acid (GABA) A receptor, beta 1 5.22 0.020435079 NB AC013268.3 5.2 0.009041786 NB RP11-696L21.1 5.18 0.026859197 NB RP11-450I19.2 5.15 0.010626103 NB TRIM9 tripartite motif containing 9 5.12 0.022360081 NB GFRA3 GDNIF family receptor alpha 3 5.11 0.015027152 NB XIRP2 xin actin-binding repeat containing 2 5.1 0.009662367 NB RHO rhodopsin 5.1 0.029762656 NB CLDN1 claudin 1 5.09 0.022360081 NB IRGC immunity-related GTPase family, cinema 5.09 0.016120921 NB PCK1 phosphoenolpyruvate carboxykinase 1 (soluble) 5.04 0.023851247 NB MAPK10 mitogen-activated protein kinase 10 5.03 0.024328524 NB EPHA6 EPH receptor A6 5.02 0.010347516 NB NXF2B nuclear RNA export factor 2B 5.02 0.026302018 NB HMGA2 high mobility group AT-hook 2 5 0.045638568 NB KLK13 kallikrein-related peptidase 13 5 0.010808151 NB RP1-14D6.2 5 0.014679168 NB C21orf90 4.93 0.008608265 NB RP11-678B3.1 4.91 0.007605535 NB CHRNA1 cholinergic receptor, nicotinic, alpha 1 (muscle) 4.9 0.02052367 NB RP11-501I19.4 4.88 0.027988697 NB GABRR1 gamma-aminobutyric acid (GABA) A receptor, rho 1 4.88 0.003640543 NB DKK3 dickkopf WNT signaling pathway inhibitor 3 4.87 0.003059735 NB RP11-1236K1.8 4.86 0.00729215 NB CHRNA9 cholinergic receptor, nicotinic, alpha 9 (neuronal) 4.82 0.045821322 NB TSPEAR-AS1 TSPEAR antisense RNA 1 4.82 0.022558878 NB NBEAP3 neurobeachin pseudogene 3 4.81 0.003673452 NB AC093162.3 4.79 0.023511088 NB LRRC37A11P leucine rich repeat containing 37, member A11, pseud 

4.77 0.002176072 NB RP11-318M2.2 4.76 0.004790916 NB RP11-760D2.10 4.75 0.025811031 NB MGP matrix Gla protein 4.73 0.008917729 NB MYH8 myosin, heavy chain 8, skeletal muscle, perinatal 4.73 0.004290131 NB RFPL4B ret finger protein-like 4B 4.7 0.020204306 NB CTD-2314B22.2 4.69 0.008917729 NB RP11-439H8.4 4.67 0.010924889 NB RP11-72K17.1 4.66 0.014141242 NB MYO5B myosin VB 4.66 0.031092971 NB CAPN9 calpain 9 4.63 0.013235921 NB OR51B6 olfactory receptor, family 51, subfamily B, member 6 4.63 0.007839036 NB PRIMA1 proline rich membrane anchor 1 4.63 0.006390779 NB DNAJC12 DnaJ (Hsp40) homolog, subfamily C, member 12 4.62 0.005329798 NB LRRC14B leucine rich repeat containing 14B 4.61 0.047474072 NB AGR2 anterior gradient 2 4.59 0.032737245 NB EGF epidermal growth factor 4.58 0.013100955 NB KRT8P19 keratin 8 pseudogene 19 4.57 0.015640563 NB FLRT3 fibronectin leucine rich transmembrane protein 3 4.55 0.00657893 NB AC005009.2 4.53 0.017521647 NB MYH7 myosin, heavy chain 7, cardiac muscle, beta 4.53 0.016408594 NB RP11-106M7.4 4.5 0.003500427 NB NDP Norrie disease (pseudoglioma) 4.5 0.029382731 NB LINC00086 4.48 0.016398129 NB SV2A synaptic vesicle glycoprotein 2A 4.47 0.024328524 NB TEKT4 tektin 4 4.46 0.004092549 NB STRA8 stimulated by retinoic acid 8 4.44 0.015103445 NB KCNIP1 Kv channel interacting protein 1 4.43 0.018812935 NB RP11-373N22.4 4.41 0.025869773 NB SERPINA3 serpin peptidase inhibitor, clade A (alpha-1 anti protein 

4.41 0.042370292 NB HMGB3P2 high mobility group box 3 pseudogene 2 4.41 0.01102242 NB MEGF10 multiple EGF-like-domains 10 4.4 0.005329798 NB RP11-342H21.2 4.39 0.047474072 NB C1QTNF3 C1q and tumor necrosis factor related protein 3 4.38 0.001483816 NB SYNDIG1L synapse differentiation inducing 1-like 4.36 0.020204306 NB USP17L2 ubiquitin specific peptidase 17-like family member 2 4.35 0.039288394 NB RP11-81K13.1 4.35 0.019520722 NB RP11-187E13.2 4.35 0.036367629 NB C12orf56 4.33 0.02678915 NB HNF4A hepatocyte nuclear factor 4, alpha 4.32 0.023187328 NB XXbac-B33L19.3 4.32 0.028569961 NB IGLON5 IgLON family member 5 4.3 0.028071732 NB HTR3B 5-hyd roxytrypta mine (serotonin) receptor 3B, ionotrop 

4.29 0.049216823 NB RP11-146E13.2 4.28 0.002988917 NB RP11-160H12.3 4.27 0.019371037 NB TMPRSS11F transmembrane protease, serine 11F 4.26 0.016219299 NB IGFBP2 insulin-like growth factor binding protein 2, 36 kDa 4.25 0.001148356 NB MIR584 microRNA 584 4.25 0.033545013 NB GPR158 G protein-coupled receptor 158 4.24 0.017221389 NB ZNF334 zinc finger protein 334 4.24 0.049100171 NB Y_RNA 4.23 0.026859197 NB FREM1 FRAS1 related extracellular matrix 1 4.22 0.014371388 NB CNDP1 carnosine dipeptidase 1 (metallopeptidase M20 family) 4.21 0.045638568 NB NR1H4 nuclear receptor subfamily 1, group H, member 4 4.2 0.014367798 NB CXorf49 4.2 0.04941826 NB MRGPRX3 MAS-related GPR, member X3 4.18 0.007254752 NB SLC22A24 solute carrier family 22, member 24 4.18 0.032272104 NB RBPJP5 RBPJ pseudogene 5 4.15 0.042283368 NB SSX6 synovial sarcoma, X breakpoint 6 (pseudogene) 4.13 0.004509166 NB PNMAL1 paraneoplastic Ma antigen famiy-like 1 4.12 0.003839527 NB CTB-35F21.4 4.11 0.043653892 NB CNN2P2 calponin 2 pseudogene 2 4.09 0.025644286 NB SALL1 spat-like transcription factor 1 4.09 0.049100171 NB PCSK1 proprotein convertase subtilisin/kexin type 1 4.08 0.003059735 NB PLA2G1B phospholipase A2, group IB (pancreas) 4.08 0.028780815 NB RP3-525N14.2 4.08 0.012492516 NB PHBP13 prohibitin pseudogene 13 4.07 0.049633437 NB PATE1 prostate and testis expressed 1 4.04 0.017521647 NB SORCS2 sortilin-related VPS10 domain containing receptor 2 4.03 0.039288394 NB EPS8L3 EPS8-like 3 4.02 0.043875977 NB SLC22A6 solute carrier famiy 22 (organic anion transporter), me 

  4.02 0.029762656 NB AC009237.9 4 0.026579731 NB CER1 cerberus 1, DAN family BMP antagonist 4 0.033575171 NB RPL17P26 ribosomal protein L17 pseudogene 26 3.99 0.006656541 NB HOXD13 homeobox D13 3.98 0.00657893 NB RP5-886K2.1 3.96 0.008079629 NB CCDC75P1 coiled-coil domain containing 75 pseudogene 1 3.96 0.049851912 NB EMILIN1 elastin microfibril interfacer 1 3.95 0.011925792 NB SULT1C3 sulfotransferase family, cytosolic, 1C, member 3 3.95 0.031076174 NB PNPLA1 patatin-like phospholipase domain containing 1 3.95 0.006706195 NB RP11-803B1.1 3.94 0.008184312 NB OTOL1 otolin 1 3.94 0.033214335 NB USP17L7 ubiquitin specific peptidase 17-like family member 7 3.93 0.031092971 NB CABP4 calcium binding protein 4 3.93 0.033656613 NB RP11-93I21.1 3.92 0.033351877 NB RP11-732A19.6 3.92 0.003430441 NB TNMD tenomodulin 3.92 0.02857165 NB SLC35D3 solute carrier family 35, member D3 3.91 0.001964064 NB KB-1980E6.3 3.91 0.006947328 NB CSMD3 CUB and Sushi multiple domains 3 3.89 0.00175507 NB RP11-138E16.2 3.89 0.00984494 NB RP11-281O15.4 3.87 0.019304276 NB MMP16 matrix metallopeptidase 16 (membrane-inserted) 3.87 0.010840451 NB MYOG myogenin (myogenic factor 4) 3.86 0.014445675 NB KCNK16 potassium channel, subfamily K, member 16 3.86 0.012777747 NB GJE1 gap junction protein, epsilon 1, 23 kDa 3.85 0.030508943 NB OR51K1P olfactory receptor, family 51, subfamily K, member 1 p 

3.85 0.004668469 NB TNN tenascin N 3.84 0.002421425 NB CFI complement factor I 3.84 0.002724323 NB GRIA4 glutamate receptor, ionotropic, AMPA 4 3.83 0.004282816 NB CTD-3049M7.1 3.83 0.028374775 NB RP5-1022P6.6 3.83 0.025822313 NB UBXN10 UBX domain protein 10 3.82 0.033880884 NB SPZ1 spermatogenic leucine zipper 1 3.82 0.019575576 NB GJD4 gap junction protein, delta 4, 40.1 kDa 3.82 0.035979007 NB ALLC allantoicase 3.8 0.029299564 NB CRP C-reactive protein, pentraxin-related 3.79 0.030546079 NB SSPO SCO-spondin 3.78 0.049100171 NB ARTN artemin 3.77 0.024375591 NB RP11-15J10.3 3.77 0.045296878 NB THSD4 thrombospondin, type I, domain containing 4 3.77 0.017221389 NB TRPM3 transient receptor potential cation channel, subfamily 

3.76 0.036386177 NB RBBP4P4 retinoblastoma binding protein 4 pseudogene 4 3.74 0.043902532 NB RP11-451K18.7 3.74 0.049851912 NB EDDM3B epididymal protein 3B 3.74 0.027138346 NB SNORA27 small nucleolar RNA, H/ACA box 27 3.73 0.043653892 NB BPIFB1 BPI fold containing family B, member 1 3.73 0.031990541 NB OLFM3 olfactomedin 3 3.72 0.008620126 NB USP17L6P ubiquitin specific peptidase 17-like family member 6, p 

3.72 0.005926234 NB GABRG2 gamma-aminobutyric acid (GABA) A receptor, gamma 

3.72 0.011960052 NB AL137067.1 3.72 0.02857165 NB KRT8P11 keratin 8 pseudogene 11 3.72 0.02857165 NB TEKT2 tektin 2 (testicular) 3.71 0.005760347 NB RNASE3 ribonuclease, RNase A family, 3 3.71 0.014391143 NB GPC4 glypican 4 3.71 0.039288394 NB KLF17 Kruppel-like factor 17 3.7 0.009594634 NB CNGB3 cyclic nucleotide gated channel beta 3 3.69 0.004030313 NB AF165138.7 3.69 0.041042494 NB EFHC2 EF-hand domain (C-terminal) containing 2 3.69 0.042306582 NB GAP43 growth associated protein 43 3.68 0.012569126 NB RETN resistin 3.68 0.040365068 NB LIMCH1 LIM and calponin homology domains 1 3.67 0.033656613 NB AC005754.1 3.67 0.049100171 NB CTCFL CCCTC-binding factor (zinc finger protein)-like 3.67 0.010416999 NB ADCY5 adenylate cyclase 5 3.66 0.036386177 NB BMPER BMP binding endothelial regulator 3.66 0.010840451 NB RP11-1081K18.1 3.66 0.030404894 NB IGFBP3 insulin-like growth factor binding protein 3 3.65 0.001483816 NB CYP7B1 cytochrome P450, family 7, subfamily B, polypeptide 1 3.65 0.002148321 NB RP11-432I13.1 3.63 0.007302655 NB CTD-2206G10.2 3.62 0.027138346 NB CACNA1S calcium channel, voltage-dependent, L type, alpha 1S s 

3.61 0.014762458 NB PDGFA platelet-derived growth factor alpha polypeptide 3.61 0.001306624 NB BPI bactericidal/permeability-increasing protein 3.61 0.004949546 NB GPR87 G protein-coupled receptor 87 3.6 0.034369721 NB WNK4 WNK lysine deficient protein kinase 4 3.6 0.031092971 NB RP11-791G16.2 3.59 0.047168612 NB CYP2C9 cytochrome P450, family 2, subfamily C, polypeptide 9 3.57 0.033515231 NB SRP68P2 signal recognition particle 68 kDa pseudogene 2 3.57 0.01262029 NB ASIC5 acid-sensing (proton-gated) ion channel family membe 

3.56 0.005369816 NB SLC18A1 solute carrier family 18 (vesicular monoamine transpor 

3.56 0.006479884 NB OR51M1 olfactory receptor, family 51, subfamily M, member 1 3.55 0.00713094 NB LA16c-60H5.7 3.55 0.005926234 NB KCNG3 potassium voltage-gated channel, subfamily G, membe 

3.54 0.036500639 NB GNGT1 guanine nucleotide binding protein (G protein), gamma 

3.53 0.042437855 NB IAPP islet amyloid polypeptide 3.53 0.016120921 NB ATP10B ATPase, class V, type 10B 3.52 0.031092971 NB ATP1B2 ATPase, Na+/K+ transporting, beta 2 polypeptide 3.51 0.028688235 NB FOXE3 forkhead box E3 3.5 0.014251282 NB ANKRD20A4 ankyrin repeat domain 20 family, member A4 3.5 0.015742933 NB RP11-496I2.2 3.5 0.019899858 NB HOTAIRM1 HOXA transcript antisense RNA, myeloid-specific 1 3.49 0.009381276 NB ZNF806 zinc finger protein 806 3.47 0.024662434 NB HIST1H1T histone cluster 1, H1t 3.47 0.010509409 NB TSPAN5 tetraspanin 5 3.46 0.003059735 NB RP11-586K2.1 3.46 0.017221389 NB FAM75C2 SPATA31 subfamily C, member 2 3.46 0.028688235 NB RP11-181D18.2 3.45 0.024790121 NB SETP9 SET pseudogene 9 3.44 0.031216315 NB CYP27C1 cytochrome P450, family 27, subfamily C, polypeptide 

3.44 0.011925792 NB SLC4A9 solute carrier famiy 4, sodium bicarbonate cotransport 

3.43 0.000583885 NB SMAD9 SMAD family member 9 3.4 0.02643572 NB GAL3ST1 galactose-3-O-sulfotransferase 1 3.4 0.03791799 NB MAGEB17 melanoma antigen family B, 17 3.4 0.034334741 NB NKX3-2 NK3 homeobox 2 3.39 0.016371906 NB PEX5L peroxisomal biogenesis factor 5-like 3.38 0.031092971 NB OR51J1 olfactory receptor, family 51, subfamily J, member 1 (g 

3.38 0.036189278 NB PTCHD2 patched domain containing 2 3.37 0.00731008 NB TMPRSS12 transmembrane (C-terminal) protease, serine 12 3.37 0.022558878 NB CORO2B coronin, actin binding protein, 2B 3.37 0.008917729 NB NINL ninein-like 3.37 0.005926234 NB PHBP5 prohibitin pseudogene 5 3.36 0.009175608 NB SDAD1P2 SDA1 domain containing 1 pseudogene 2 3.36 0.028426013 NB RP11-645N11.2 3.35 0.000869748 NB SLC22A17 solute carrier family 22, member 17 3.35 0.003839527 NB FAM106A family with sequence similarity 106, member A 3.35 0.014371388 NB SOX9 SRY (sex determining region Y)-box 9 3.35 0.042370292 NB AKR1B1P1 aldehyde reductase family 1, member B1 pseudogene 

3.34 0.049100171 NB ABCC8 ATP-binding cassette, sub-family C (CFTR/MRP), memb 

3.34 0.023867249 NB ZNF541 zinc finger protein 541 3.34 0.015742933 NB RP11-136I13.1 3.33 0.017952081 NB RP11-732A19.5 3.33 0.028688235 NB CLEC1A C-type lectin domain family 1, member A 3.33 0.005926234 NB NRXN1 neurexin 1 3.32 0.042306582 NB MIR581 microRNA 581 3.32 0.012651023 NB DLEU7 deleted in lymphocytic leukemia, 7 3.32 0.019413544 NB RP11-355N15.1 3.32 0.045518278 NB RP11-111F5.2 3.31 0.019674294 NB KCNC2 potassium voltage-gated channel, Shaw-related subfam 

3.31 0.0064423 NB AMHR2 anti-Mullerian hormone receptor, type II 3.3 0.002397768 NB SLC2A12 solute carrier family 2 (facilitated glucose transporter), 

3.28 0.004495465 NB C9orf170 3.28 0.01142727 NB AC012531.25 3.28 0.01659065 NB LIPI lipase, member I 3.28 0.035096859 NB PCDHGA12 protocadherin gamma subfamily A, 12 3.27 0.049100171 NB MIPEPP1 mitochondrial intermediate peplidase pseudogene 1 3.27 0.02019187 NB PPP4R4 protein phosphatase 4, regulatory subunit 4 3.27 0.046776361 NB GOLGA6L11P golgin A6 family-like 11, pseudogene 3.27 0.000599951 NB AC000110.1 3.26 0.016753819 NB CHRM4 cholinergic receptor, muscarinic 4 3.26 0.011041252 NB BX004987.3 3.24 0.049638568 NB RP11-744D14.1 3.24 0.003003823 NB CSRP3 cysteine and glycine-rich protein 3 (cardiac LIM protein 

3.23 0.009241778 NB NPAS3 neuronal PAS domain protein 3 3.22 0.00657893 NB WNT3 wingless type MMTV integration site family, member 3 3.22 0.013811098 NB RP11-496I2.5 3.2 0.010840451 NB RP3-352A20.1 3.19 0.002176072 NB SYT1 synaptotagmin I 3.19 0.036500639 NB SEC14L4 SEC14-like 4 (S. cerevisiae) 3.19 0.047474072 NB CELA2A chymotrypsin-like elastase family, member 2A 3.18 0.016408594 NB CTD-2158P22.1 3.18 0.023867249 NB PDE6A phosphodiesterase 6A, cGMP-specific, rod, alpha 3.18 0.007320475 NB TBX3 T-box 3 3.18 0.001007228 NB ABCA8 ATP-binding cassette, sub-family A (ABC1), member 8 3.18 0.049100171 NB PCDHB2 protocadherin beta 2 3.16 0.008917729 NB DRD2 dopamine receptor D2 3.16 0.019111626 NB ALS2CR11 amyotrophic lateral sclerosis 2 (juvenile) chromosome 3.15 0.02052367 NB RP11-510H23.1 3.15 0.017138695 NB FAM194B glutamate-rich 6B 3.15 0.045518278 NB KCNJ3 potassium inwardly-rectifying channel, subfamily J, me 

3.13 0.002347701 NB DZIP1 DAZ interacting zinc finger protein 1 3.12 0.036386177 NB HIF3A hypoxia inducible factor 3, alpha subunit 3.12 0.024328524 NB SLC17A3 solute carrier family 17 (organic anion transporter), me 

3.11 0.038991906 NB RP11-1134I14.2 3.11 0.019371037 NB RP11-1396O13.8 3.1 0.048226887 NB RP11-307I2.1 3.1 0.009325595 NB RP11-114H24.5 3.1 0.039288394 NB AC020907.2 3.1 0.047474072 NB AC107021.1 3.09 0.025748667 NB GYPE glycophorin E (MNS blood group) 3.09 0.02287369 NB SALL4 spalt-like transcription factor 4 3.09 0.033656613 NB SPAG17 sperm associated antigen 17 3.08 0.009839457 NB AFF3 AF4/FMR2 family, member 3 3.07 0.039288394 NB TDGF1 teratocarcinoma-derived growth factor 1 3.07 0.049369302 NB STK19P 3.07 0.000676183 NB SFTPA1 surfactant protein A1 3.06 0.033575171 NB SNAI1 snail family zinc finger 1 3.06 0.00657893 NB AC092155.2 3.05 0.047995343 NB RAPGEF4 Rap guanine nucleotide exchange factor (GEF) 4 3.05 0.02052367 NB AKR1B15 aldo-keto reductase family 1, member B15 3.05 0.033277256 NB ADAMTS7 ADAM metallopeptidase with thrombospondin type 1 r 

3.05 0.008917729 NB COLEC12 collectin sub-family member 12 3.05 0.045638568 NB PTGS2 prostaglandin-endoperoxide synthase 2 (prostaglandin 

3.04 0.039288394 NB ULBP3 UL16 binding protein 3 3.04 0.010509409 NB HMGB3P31 high mobility group box 3 pseudogene 31 3.04 0.020318802 NB AQP7P1 aquaporin 7 pseudogene 1 3.03 0.039288394 NB ABCC6P2 ATP-binding cassette, sub-family C, member 6 pseudog 

3.03 0.039234101 NB ZNF331 zinc finger protein 331 3.03 7.63E−05 NB KY kyphoscoliosis peptidase 3.02 0.04213223 NB GS1-184P14.1 3.01 0.01305666 NB DMD dystrophin 3 0.02643572 NB AC079354.1 2.99 0.000590409 NB MS4A3 membrane-spanning 4-domains, subfamily A, member 

2.99 0.021446576 NB C14orf57 2.99 0.039234101 NB C14orf132 2.99 0.033656613 NB MSTN myostatin 2.98 0.021083625 NB AL772307.1 2.98 0.016310813 NB PIEZO2 piezo-type mechanosensitive ion channel component 2 2.98 0.013100955 NB ZNF355P zinc finger protein 355, pseudogene 2.98 0.010441837 NB KLK14 kallikrein-related peptidase 14 2.97 0.021373132 NB MACROD2 MACRO domain containing 2 2.97 0.024328524 NB RP11-521J5.1 2.96 0.031092971 NB TLX2 T-cell leukemia homeobox 2 2.95 0.04488914 NB RPL7AP26 ribosomal protein L7a pseudogene 25 2.95 0.036500639 NB MOXD1 monooxygenase, DBH-like 1 2.95 0.02643572 NB RP5-1198O20.4 2.94 0.027941793 NB RP11-190P13.1 2.94 0.025784335 NB SOSTDC1 sclerostin domain containing 1 2.94 0.02875596 NB HCAR1 hydroxycarboxylic acid receptor 1 2.94 0.015249492 NB TCP11 t-complex 11, testis-specific 2.93 0.012073496 NB FXYD1 FXYD domain containing ion transport regulator 1 2.93 0.022360081 NB C7orf61 2.92 0.012651023 NB DDX25 DEAD (Asp-Glu-Ala-Asp) box helicase 25 2.92 0.035185369 NB OXTR oxytocin receptor 2.91 0.011547361 NB FAM75A1 SPATA31 subfamily A, member 1 2.91 0.012492516 NB AC016251.1 2.91 0.012118209 NB AC008079.9 2.91 0.039259375 NB MIR548I1 microRNA 548i-1 2.89 0.039934696 NB RP11-510H23.3 2.89 0.019413544 NB RPS20P22 ribosomal protein S20 pseudogene 22 2.89 0.035096859 NB C1orf173 2.88 0.03877208 NB HIGD1AP9 HIG1 hypoxia inducible domain family, member 1A pse 

2.88 0.008789839 NB ST13P12 suppression of tumorigenicity 13 (colon carcinoma) (Hs 

2.87 0.0049729 NB RP11-15J10.8 2.87 0.020318802 NB DCHS1 dachsous cadherin-related 1 2.87 0.02643572 NB TAF7L TAF7-like RNA polymerase II, TATA box binding protein 2.87 0.027941793 NB RP11-1286E23.6 2.86 0.036386177 NB RP11-798K3.4 2.86 0.031076174 NB AC073264.10 2.85 0.032737245 NB CMYA5 cardiomyopathy associated 5 2.84 0.018812935 NB HOXA3 homeobox A3 2.84 0.033656613 NB RP11-812E19.6 2.83 0.015742933 NB UBE2U ubiquitin-conjugating enzyme E2U (putative) 2.82 0.025644286 NB RP11-277P12.20 2.82 0.019058997 NB CBLN4 cerebellin 4 precursor 2.82 0.026146007 NB RP11-146D12.2 2.81 0.042370292 NB PRSS55 protease, serine, 55 2.8 0.028426013 NB RTDR1 2.8 0.033575171 NB EPHA2 EPH receptor 42 2.78 0.014371388 NB ULBP2 UL16 binding protein 2 2.78 0.036386177 NB SPEM1 spermatid maturation 1 2.78 0.023187328 NB KRT20 keratin 20 2.78 0.012799782 NB RP11-325P15.1 2.77 0.031092971 NB LONRF2 LON peptidase N-terminal domain and ring finger 2 2.77 0.022360081 NB CDH10 cadherin 10, type 2 (T2-cadherin) 2.77 0.016475123 NB SORCS3 sortilin-related VPS10 domain containing receptor 3 2.77 0.003476545 NB ARHGAP40 Rho GTPase activating protein 40 2.77 0.00654708 NB HOXA2 homeobox A2 2.76 0.013100955 NB C12orf50 2.76 0.014949579 NB FAM19A1 family with sequence similarity 19 (chemokine (C-C mo 

2.75 0.019074797 NB RP11-695J4.2 2.75 0.017818411 NB CTD-2201I18.1 uncharacterized LOC101929215 2.74 0.02643572 NB CLDN2 claudin 2 2.74 0.016310813 NB PRRX1 paired related homeobox 1 2.73 0.042370292 NB FAM46A family with sequence similarity 46, member A 2.73 0.003059735 NB CACNA2D4 calcium channel, voltage-dependent, alpha 2/delta sub 

2.73 0.049100171 NB RP11-400L8.2 2.72 0.017559073 NB ASS1P7 argininosurxinate synthetase 1 pseudogene 7 2.72 0.024493172 NB NDST4 N-deacetylase/N-sulfatransferase (heparan glucosamin 

2.72 0.03781544 NB KB-1554H10.1 2.72 0.019058997 NB NYNRIN NYN domain and retroviral integrase containing 2.72 0.036386177 NB CADM4 cell adhesion molecule 4 2.72 0.008070194 NB GABRB2 gamma-aminobutyric acid (GABA) A receptor, beta 2 2.71 0.00731008 NB HEPACAM hepatic and glial cell adhesion molecule 2.71 0.02247963 NB RP11-903H12.2 2.71 0.027650005 NB CTA-211A9.5 2.71 0.006592317 NB BHLHB9 basic helix-loop-helix domain containing, class B, 9 2.71 0.005329798 NB RP11-157D18.2 2.7 0.020318802 NB RP11-317B7.2 2.7 0.038991906 NB FAM198B family with sequence similarity 198, member B 2.7 0.015742933 NB FAM81B family with sequence similarity 81, member B 2.7 0.042306582 NB RCAN2 regulator of calcineurin 2 2.7 0.022360081 NB RP11-533F5.2 2.69 0.025144552 NB RP11-597D13.9 2.69 0.022360081 NB KLHL31 kelch-like family member 31 2.69 0.031835936 NB EIF3EP1 eukaryotic translation initiation factor 3, subunit E pse 

2.69 0.000438786 NB MLLT11 myeloid/lymphoid or mixed-lineage leukemia (trithora 

2.68 0.003430441 NB SERPINC1 serpin peptidase inhibitor, clade C (antithrombin), me 

2.68 0.004785714 NB RP11-280F2.1 2.68 0.00713094 NB PCDHGA3 protocadherin gamma subfamily A, 3 2.68 0.003839527 NB SPRY4 sprouty homolog 4 (Drosophila) 2.68 0.039288394 NB BMP6 bone morphogenetic protein 6 2.68 0.008070194 NB SSU72P8 SSU72 pseudogene 8 2.68 0.006562428 NB PEX5L-AS1 PEX5L antisense RNA 1 2.66 0.033545013 NB LRP4 low density lipoprotein receptor-related protein 4 2.66 0.011925792 NB NPM1P8 nucleophosmin 1 (nucleolar phosphoprotein B23, num 

2.66 0.027941793 NB SHROOM1 shroom family member 1 2.65 0.008070194 NB HMGN2P10 high mobility group nucleasomal binding domain 2 pse 

2.65 0.045518278 NB DGAT2L6 diacylglycerol O-acyltransferase 2-like 6 2.65 0.018415671 NB RP11-944L7.4 2.64 0.040821352 NB OTOP1 otopetrin 1 2.64 0.03495366 NB PCDHGC3 protocadherin gamma subfamily C, 3 2.64 0.02643572 NB GSG1 germ cell associated 1 2.64 0.001853615 NB VWA3A von Willebrand factor A domain containing 3A 2.64 0.0186415 NB LMOD3 leiomodin 3 (fetal) 2.63 0.01785722 NB PIRT phosphoinositide-interacting regulator of transient rec 

2.63 0.00447648 NB RPL36P4 ribosomal protein L36 pseudogene 4 2.63 0.007320475 NB THBS4 thrombospondin 4 2.62 0.049100171 NB RP11-482D24.3 2.62 0.013181478 NB SULT1A1 sulfotransferase family, cytosolic, 1A, phenol-preferrin 

2.62 0.018812935 NB CEACAM8 carcinoembryonic antigen-related cell adhesion molec 

2.62 0.02287369 NB LNX1 ligand of numb-protein X 1, E3 ubiquitin protein ligase 2.61 0.014371388 NB GRM7 glutamate receptor, metabotropic 7 2.6 0.020255042 NB RP11-651P23.2 2.6 0.029382731 NB AC097467.2 2.6 0.033794271 NB DBX2 developing brain homeobox 2 2.6 0.003036454 NB AL445989.1 2.6 0.03995294 NB TEKT5 tektin 5 2.6 0.016408594 NB CAGE1 cancer antigen 1 2.59 0.012569126 NB OR52E6 olfactory receptor, family 52, subfamily E, member 6 2.59 0.016753819 NB CTD-2314B22.3 2.59 0.004785714 NB ZNF177 zinc finger protein 177 2.59 0.045638568 NB AP000281.1 2.59 0.043523654 NB CELA2B chymotrypsin-like elastase family, member 2B 2.58 0.001487356 NB LHCGR luteinizing hormone/choriogonadotropin receptor 2.58 0.039288394 NB GRID2 glutamate receptor, ionotropic, delta 2 2.58 0.019899858 NB LRRC17 leucine rich repeat containing 17 2.58 0.001483816 NB OR51I2 olfactory receptor, family 51, subfamily I, member 2 2.58 0.007916312 NB RP11-166D19.1 2.58 0.023509294 NB ZDHHC22 zinc finger, DHHC-type containing 22 2.58 0.009476909 NB KSR1 kinase suppressor of ras 1 2.58 0.014371388 NB EMID1 EMI domain containing 1 2.58 0.018812935 NB OR6K3 olfactory receptor, family 6, subfamily K, member 3 2.57 0.039717587 NB SLC38A3 solute carrier family 38, member 3 2.57 0.04352477 NB B3GALNT1 beta-1,3-N-acetylgalactosaminyltransferase 1 (globosid 

2.57 0.033656613 NB CTD-2337A12.1 2.57 0.019575576 NB GALNT8 polypeptide N-acetylgalactosa minyltransferase 8 2.57 0.033656613 NB SAGE1 sarcoma antigen 1 2.57 0.030546079 NB OR52D1 olfactory receptor, family 52, subfamily D, member 1 2.56 0.029028339 NB ALX4 ALX homeobox 4 2.56 0.009204866 NB KCNMB4 potassium large conductance calcium-activated channe 

2.56 0.036386177 NB AL589743.1 2.56 0.001007228 NB AP000322.53 2.56 0.016371906 NB HBXIPP1 2.55 0.024542839 NB CHN1 chimerin 1 2.55 0.028688235 NB TACR3 tachykinin receptor 3 2.55 0.011399948 NB AC008265.2 2.55 0.033214335 NB STRADBP1 STE20-related kinase adaptor beta pseudogene 1 2.55 0.011576251 NB C9orf57 2.55 0.019540488 NB DPF3 D4, zinc and double PHD fingers, famiy 3 2.55 0.039288394 NB GOLGA6B golgin A6 family, member B 2.55 0.039316473 NB GNAS-AS1 GNAS antisense RNA 1 2.55 0.000379081 NB RP13-140E4.1 2.55 0.021446576 NB LL0XNC01-1161E7.1 2.55 0.02857165 NB OR51I1 olfactory receptor, family 51, subfamily I, member 1 2.54 0.015079112 NB UNC13C unc-13 homolog C (C. elegans) 2.54 0.04694431 NB RP11-1079K10.1 2.54 0.038228592 NB GOLGA6L16P golgin A6 family-like 16, pseudogene 2.54 0.017521647 NB MMEL1 membrane metallo-endopeptidase-like 1 2.53 0.027650005 NB CTD-2330J20.2 2.53 0.020779381 NB RRM2P3 ribonucleotide reductase M2 polypeptide pseudogene 2.53 0.021040385 NB AGTR1 angiotensin II receptor, type 1 2.52 0.039316473 NB RELN reelin 2.52 0.02052367 NB HMGN1P18 high mobility group nudeasome binding domain 1 pse 

2.52 0.035185369 NB ANGPT1 angiopoietin 1 2.52 0.024328524 NB GRIK1 glutamate receptor, ionotropic, kainate 1 2.52 0.000881664 NB RP11-267N12.3 2.51 0.003839527 NB KIAA1239 NACHT and WD repeat domain containing 2 2.51 0.00099915 NB AGBL3 ATP/GTP binding protein-like 3 2.51 0.024328524 NB RP11-32B5.2 2.51 0.028184742 NB ATP2B3 ATPase, Ca++ transporting, plasma membrane 3 2.51 0.033698056 NB TAS1R1 taste receptor, type 1, member 1 2.5 0.017138695 NB ANKRD20A14P ankyrin repeat domain 20 family, member A14, pseudo 

2.5 0.049100171 NB RGS5 regulator of G-protein signaling 5 2.5 0.002421425 NB SOWAHA sosondowah ankyrin repeat domain family member A 2.5 0.030546079 NB OR52E4 olfactory receptor, family 52, subfamily E, member 4 2.5 0.023557449 NB ANO3 anoctamin 3 2.5 0.02019187 NB TMEFF1 transmembrane protein with EGF-like and two follistati 

2.49 0.005477973 NB C12orf28 2.49 0.035978444 NB CORIN corin, serine peptidase 2.48 0.033656613 NB RP11-309L24.6 2.48 0.014969485 NB SYNM synemin, intermediate filament protein 2.48 0.003059735 NB PDHA2 pyruvate dehydrogenase (lipoamide) alpha 2 2.47 0.015181716 NB ANGPT2 angiopcietin 2 2.47 0.004785714 NB S1PR3 sphingosine-1-phosphate receptor 3 2.47 0.031092971 NB ANKRD20A8P ankyrin repeat domain 20 family, member A8, pseudog 

2.46 0.031092971 NB OBP2B odorant binding protein 2B 2.46 0.046783458 NB HHEX hematopoietically expressed homeobox 2.46 0.008070194 NB AC007731.1 2.46 0.045238769 NB CLCN4 chloride channel, voltage-sensitive 4 2.46 0.018812935 NB HSPA7 heat shock 70 kDa protein 7(HSP70B) 2.45 0.031092971 NB C7orf58 2.45 0.022360081 NB ANKRD20A3 ankyrin repeat domain 20 family, member A3 2.45 0.028688235 NB C2orf66 2.44 0.024790121 NB OR56B4 olfactory receptor, family 56, subfamily B, member 4 2.44 0.020968365 NB PCDHGB1 protocadherin gamma subfamily B, 1 2.43 0.022360081 NB RP1-97D16.1 2.43 0.02857165 NB PPP1R9A protein phosphatase 1, regulatory subunit 9A 2.43 0.036386177 NB TMC5 transmembrane channel-like 5 2.43 0.033351877 NB TEX11 testis expressed 11 2.43 0.01305666 NB PADI6 peptidyl arginine deiminase, type VI 2.42 0.048733769 NB RP11-481K9.4 2.42 0.0186415 NB RP11-496I2.6 2.42 0.009839457 NB RP11-310A13.2 2.41 0.01373806 NB RP1-66E7.1 2.41 0.045812142 NB RP11-463J10.2 2.41 0.031092971 NB SULT1C4 sulfotransferase family, cytosolic, 1C, member 4 2.4 0.003430441 NB AC073629.2 2.4 0.025822313 NB CTD-2349P21.1 2.4 0.002682049 NB TCN1 transcobalamin I (vitamin B12 binding protein, R binde 

2.39 0.039288394 NB SYT16 synaptotagmin XVI 2.39 0.00346671 NB RP11-454K24.1 2.39 0.007806012 NB SLC35G2 solute carrier farniy 35, member G2 2.38 0.028688235 NB RP11-321E8.1-001 2.38 0.002608342 NB RP11-6O2.4 2.38 0.003839527 NB HSPA6 heat shock 70 kDa protein 6 (HSP70B′) 2.37 0.024328524 NB RP11-136C24.1 2.37 0.042079896 NB AC073343.1 2.37 0.004185714 NB GAGE10 G antigen 10 2.37 0.047897625 NB ANKRD20A2 ankyrin repeat domain 20 family, member A2 2.36 0.022360081 NB DUSP13 dual specificity phosphatase 13 2.36 0.016199164 NB ITM2C integral membrane protein 2C 2.35 0.001902564 NB RP11-397E7.2 2.35 0.039148946 NB OSMR oncostatin M receptor 2.35 0.042370292 NB RP11-10F11.2 2.35 0.013831074 NB TFPI2 tissue factor pathway inhibitor 2 2.35 0.047168612 NB RP11-530N7.2 2.35 0.033852011 NB POU5F1B POU class 5 homeobox 1B 2.34 0.045478051 NB TECTA tectorin alpha 2.34 0.013100955 NB RASL10B RAS-like, family 10, member B 2.34 0.09883796 NB CYP2G1P cytochrome P450, family 2, subfamily G, polypeptide 1 2.34 0.012569126 NB RP4-610C12.4 2.34 0.009966462 NB OR11L1 olfactory receptor, family 11, subfamily L, member 1 2.33 0.029382731 NB CNTN6 contactin 6 2.33 0.031092971 NB C4orf19 2.33 0.004949546 NB YIPF7 Yip1 domain family, member 7 2.33 0.003640543 NB PCDHGC5 protocadherin gamma subfamily C, 5 2.33 0.005329798 NB ADGB androglobin 2.33 0.022638595 NB PSMC1P3 proteasome (prosome, macropain) 26S subunit, ATPas 

2.33 0.043902532 NB FGF2 fibroblast growth factor 2 (basic) 2.32 0.022360081 NB AC008537.2 2.32 0.002180177 NB CTD-2224J9.4 2.32 0.032296489 NB CSPG5 chondroitin sulfate proteoglycan 5 (neuroglycan C) 2.31 0.028688235 NB RP11-254A17.1 2.31 0.01373806 NB NACAD NAC alpha domain containing 2.31 0.031092971 NB LMOD2 leiomodin 2 (cardiac) 2.31 0.047168612 NB BAALC brain and acute leukemia, cytoplasmic 2.31 0.045638568 NB RP11-84C10.2 2.31 0.042339272 NB HNRNPA1P24 heterogeneous nuclear ribonucleoprotein A1 pseudoge 

2.3 0.017952081 NB KCNMB2 potassium large conductance calcium-activated channe 

2.3 0.02287369 NB NREP neuronal regeneration related protein 2.3 0.003430441 NB PCMTD1P3 protein-L-isoaspartate (D-aspartate) O-methyltransfera 

2.3 0.015181716 NB ADRB3 adrenoceptor beta 3 2.3 0.035978444 NB PA2G4P2 proliferation-associated 2G4 pseudogene 2 2.3 0.03877208 NB HOXD10 homeobox D10 2.29 0.002421425 NB GNG5P3 guanine nucleotide binding protein (G protein), gamma 

2.29 0.011925792 NB KCNJ8 potassium inwardly-rectifying channel, subfamily J, me 

2.29 0.02643572 NB RP11-182J1.13 2.29 0.049100171 NB LIMS3 LIM and senescent cell antigen-like domains 3 2.28 0.032616447 NB HOXA-AS2 HOXA cluster antisense RNA 2 2.28 0.028688235 NB TRPC4 transient receptor potential cation channel, subfamily 

2.28 0.02052367 NB DNER delta/notch-like EGF repeat containing 2.27 0.013528999 NB C5orf60 2.27 0.030628105 NB NECAB1 N-terminal EF-hand calcium binding protein 1 2.27 0.022828147 NB RP11-144A16.1 2.27 0.014371388 NB LINC00552 long intergenic non-protein coding RNA 552 2.27 0.04104249 NB MEG8 maternally expressed 8 (non-protein coding) 2.27 0.022042996 NB AC005562.3 2.27 0.01377845 NB NAP1L5 nucleosome assembly protein 1-like 5 2.26 0.008070194 NB NXPH1 neurexophilin 1 2.26 0.046077602 NB BBOX1 butyrobetaine (gamma), 2-oxoglutarate dioxygenase (g 

2.26 0.045478051 NB SCN4B sodium channel, voltage-gated, type IV, beta subunit 2.26 0.024328524 NB ZFP82 ZFP82 zinc finger protein 2.26 0.045638568 NB RP1-83M4.2 2.25 0.004965109 NB FABP9 fatty acid binding protein 9, testis 2.25 0.004124703 NB NEB nebulin 2.24 0.049100171 NB SPP1 secreted phosphoprotein 1 2.24 0.049100171 NB NPY6R neuropeptide Y receptor Y6 (pseudogene) 2.24 0.049100171 NB PCDHB12 protocadherin beta 12 2.24 0.002421425 NB RP1-95L4.4 2.24 0.017221389 NB C15orf26 2.24 0.02052367 NB IGSF1 immunoglobuin superfamily, member 1 2.24 0.037056891 NB COL6A4P1 collagen, type VI, alpha 4 pseudogene 1 2.23 0.030546079 NB PCDHB10 protocadherin beta 10 2.23 0.005329798 NB DPYSL3 dihydropyrimidinase-like 3 2.23 0.031092971 NB HOXA5 homeobox A5 2.23 0.005329798 NB RP11-561C5.5 2.23 0.009531305 NB AP000525.10 2.23 0.036386177 NB FOXO6 forkhead box O6 2.22 0.036386177 NB MIR571 microRNA 571 2.22 0.041739925 NB SLC22A7 solute carrier family 22 (organic anion transporter), me 

2.22 0.038448428 NB AL589743.2 2.22 0.035185369 NB DLK1 delta-like 1 homolog (Drosophila) 2.22 0.047935027 NB RP11-316M1.11 2.21 0.02643572 NB C1orf189 2.21 0.027138346 NB RP11-182J1.14 2.21 0.013100955 NB snoU2_19 2.21 0.031216315 NB GSTM3 glutathione S-transferase mu 3 (brain) 2.2 0.024328524 NB TMEM30C transmembrane protein 30C 2.2 0.019201979 NB CSGALNACT1 chondroitin sulfate N-acetylgalactosaminyltransferase 

2.2 0.004785714 NB NAP1L1P1 nucleosome assembly protein 1-like 1 pseudogene 1 2.2 0.032737245 NB RP11-522B15.6 2.2 0.04876748 NB PRAMEF15 PRAME famity member 15 2.19 0.046783458 NB HPCA hippocalcin 2.19 0.009764943 NB ISPD isoprenoid synthase domain containing 2.19 0.001483816 NB RP11-365P13.3 2.19 0.021985463 NB AL132709.8 2.19 0.045588897 NB GOLGA6A golgin A6 family, member A 2.19 0.045638568 NB AC048382.4 2.19 0.02052367 NB MYO15A myosin XVA 2.19 0.031092971 NB C1orf61 2.18 0.042306582 NB KCNJ10 potassium inwardly-rectifying channel, subfamily J, me 

2.18 0.045638568 NB TNNI1 troponin I type 1 (skeletal, slow) 2.18 0.049758592 NB SCN2A sodium channel, voltage-gated, type II, alpha subunit 2.18 0.012651023 NB NSUN7 NOP2/Sun domain family, member 7 2.18 0.049100171 NB PRSS48 protease, serine, 48 2.18 0.018812935 NB HBEGF heparin-binding EGF-like growth factor 2.18 0.001902564 NB FAM75A6 SPATA31 subfamily A, member 6 2.18 0.026579731 NB IMPDH1P11 IMP (inosine monophosphate) dehydrogenase 1 pseud 

2.18 0.037640265 NB RP11-145A3.4 2.17 0.011547361 NB 3-Mar membrane-associated ring finger (C3HC4) 3, E3 ubiquit 

2.17 0.002724323 NB CAMK2B calcium/calmodulin-dependent protein kinase II beta 2.17 0.03791799 NB C9orf171 2.17 0.005662083 NB RBM20 RNA binding motif protein 20 2.17 0.028688235 NB ASCL3 achaete-scute family bHLH transcription factor 3 2.17 0.021083625 NB PDE4B phosphodiesterase 4B, cAMP-specific 2.16 0.033656613 NB SERPINE2 serpin peptidase inhibitor, clade E (nexin, plasminogen 

2.16 0.008917729 NB PCDHGB2 protocadherin gamma subfamily B, 2 2.16 0.000280919 NB ZNF204P zinc finger protein 204, pseudogene 2.16 0.045512017 NB 14-Sep septin 14 2.16 0.013119454 NB RP11-661G16.2 2.16 0.02052367 NB SRP68P3 signal recognition particle 68 kDa pseudogene 3 2.16 0.029028339 NB NEFH neurofilament, heavy polypeptide 2.16 0.042370292 NB ADCY10 adenylate cyclase 10 (soluble) 2.15 0.002148321 NB RP11-472B18.1 2.15 0.004785714 NB RP11-673E1.3 2.15 0.004290131 NB AE000662.92 2.14 0.039148946 NB KCNMB3P1 potassium large conductance calcium-activated channe 

2.14 0.008070194 NB MIR1231 microRNA 1231 2.13 0.033553777 NB WDR64 WD repeat domain 64 2.13 0.012073496 NB AC004980.10 2.13 0.000671309 NB SLC26A3 solute carrier family 26 (anion exchanger), member 3 2.13 0.039253648 NB SNORA49 small nucleolar RNA, H/ACA box 49 2.13 0.022360081 NB ESRRB estrogen-related receptor beta 2.13 0.042306582 NB AC011551.2 2.13 0.026864606 NB ARHGAP29 Rho GTPase activating protein 29 2.12 0.039288394 NB AL583842.6 2.12 0.036386177 NB LRRC9 leucine rich repeat containing 9 2.12 0.02643572 NB NID1 nidogen 1 2.11 0.004785714 NB RP11-13J8.1 2.11 0.004220588 NB PCDHB18 2.11 0.011925792 NB ZNF679 zinc finger protein 679 2.11 0.046783458 NB RP11-959I15.1 2.11 0.02939697 NB AP000593.6 2.11 0.026579731 NB TSPY26P testis specific protein, Y-linked 26, pseudogene 2.11 0.042370292 NB FBLIM1 filamin binding LIM protein 1 2.1 0.045638568 NB PAPPA2 pappalysin 2 2.1 0.045478051 NB OFD1P17 OFD1 pseudogene 17 2.1 0.022360081 NB RP11-43D2.6 2.1 0.049100171 NB GRAMD3 GRAM domain containing 3 2.1 0.036386177 NB ICK intestinal cell (MAK-like) kinase 2.1 0.015742933 NB EPB41L2 erythrocyte membrane protein band 4.1-like 2 2.1 0.001902564 NB TUSC3 tumor suppressor candidate 3 2.1 0.02052367 NB RP11-1102P16.1 2.1 0.033545013 NB RPL19P14 ribosomal protein L19 pseudogene 14 2.1 0.005477973 NB RP11-654A16.3 2.1 0.003321047 NB TMPRSS9 transmembrane protease, serine 9 2.1 0.018812935 NB FNBP1L formin binding protein 1-like 2.09 0.005329798 NB ASNSP5 asparagine synthetase pseudogene 5 2.09 0.024790121 NB AC007272.3 2.09 0.004220588 NB PLK2 polo-like kinase 2 2.09 0.036386177 NB PLAC8L1 PLAC8-like 1 2.09 0.021985463 NB GAPDHP73 glyceraldehyde-3-phosphate dehydrogenase pseudoge 

2.09 0.039934696 NB RP11-529J17.2 2.09 0.005329798 NB MAP7D2 MAP 7 domain containing 2 2.09 0.047168612 NB ASPRV1 aspartic peptidase, retroviral-like 1 2.08 0.017221389 NB SLC10A4 solute carrier family 10, member 4 2.08 0.015740659 NB DCHS2 dachsous cadherin-related 2 2.08 0.036386177 NB PCDHB15 protocadherin beta 15 2.08 0.001681771 NB RP11-94K8.1 2.08 0.045295878 NB TMC2 transmembrane channel-like 2 2.08 0.017138695 NB CTD-2514C3.1 2.08 0.003430441 NB C3orf30 2.07 0.034606296 NB KCTD16 potassium channel tetramerization domain containing 2.07 0.035336374 NB BACH1-IT1 BACH1 intronic transcript 1 (non-protein coding) 2.07 0.000671309 NB RP11-1114A5.4 2.07 0.031092971 NB LEPR leptin receptor 2.06 0.013100955 NB PCDHB19P protocadherin beta 19 pseudogene 2.06 0.008917729 NB SPINK7 serine peptidase inhibitor, Kazal type 7 (putative) 2.06 0.021373132 NB LCTL lactase-like 2.06 0.049100171 NB AC011718.2 2.06 0.016199164 NB ZCCHC12 zinc finger, CCHC domain containing 12 2.06 0.004421152 NB RP11-1007J8.1 2.05 0.030204228 NB S100G S100 calcium binding protein G 2.05 0.011590706 NB C3orf74 2.04 0.018624954 NB NAALADL2 N-acetylated alpha-linked acidic dipeptidase-like 2 2.04 0.042370292 NB SPRY1 sprouty homolog 1, antagonist of FGF signaling (Droso 

2.04 0.003839527 NB MIR550A2 microRNA 550a-2 2.04 0.020508813 NB FAM55A neurexophilin and PC-esterase domain family, member 

2.04 0.04876748 NB SP6 Sp6 transcription factor 2.04 0.016408594 NB RP5-1068H6.3 2.04 0.017824327 NB HMGN2P23 high mobility group nucleosomal binding domain 2 pse 

2.03 0.023511088 NB PLSCR4 phospholipid scramblase 4 2.03 0.008070194 NB CTD-2292P10.4 uncharacterized LOC100288181 2.03 0.04883796 NB AQP7P2 aquaporin 7 pseudogene 2 2.03 0.047168612 NB IFLTD1 2.03 0.038978796 NB RP11-423O2.1 2.02 0.009084306 NB CCDC136 coiled-coil domain containing 136 2.02 0.005329798 NB ATP2B1 ATPase, Ca++ transporting, plasma membrane 1 2.02 0.003059735 NB ASIP agouti signaling protein 2.02 0.031092971 NB DPPA3P1 developmental pluripotency associated 3 pseudogene 

2.02 0.031391184 NB AC007563.1 2.01 0.027988697 NB SEMA5A sema domain, seven thrombospondin repeats (type 1 a 

2.01 0.033656613 NB SCARNA15 small Cajal body-specific RNA 15 2.01 0.033351877 NB TRHR thyrotropin-releasing hormone receptor 2.01 0.047168612 NB RPL7L1P12 ribosomal protein 17-like 1 pseudogene 12 2.01 0.024790121 NB RP11-138H8.5 2.01 0.039288394 NB DUSP15 dual specificity phosphatase 15 2.01 0.045638568 NB ZNF75D zinc finger protein 75D 2.01 0.02643572 NB MIR211 microRNA 211 654.53 0.003258841 CB TRGJP2 T cell receptor gamma joining P2 98.51 0.018744092 CB IGHJ2 immunoglobulin heavy joining 2 92.82 0.048733769 CB RP11-259G18.2 69.31 0.039288394 CB TRBV7-7 T cell receptor beta variable 7-7 57.74 0.00541274 CB IGKV6-21 immunoglobulin kappa variable 6-21 (non-functional) 49.85 0.037395217 CB IGHJ1 immunoglobulin heavy joining 1 44.48 0.04073483 CB AC105247.1 31.61 0.014702641 CB MIR513A2 microRNA 513a-2 30.81 0.024507002 CB FAM69C family with sequence similarity 69, member C 28.52 0.028374775 CB ZBTB40-IT1 ZBTB40 intronic transcript 1 (non-protein coding) 28.24 0.029540253 CB TRBV5-7 T cell receptor beta variable 5-7 (non-functional) 27.78 0.011689051 CB TRPM1 transient receptor potential cation channel, subfamily 

25.45 0.003430441 CB TRBV6-9 T cell receptor beta variable 6-9 25.33 0.036277389 CB IGHV3-11 immunoglobulin heavy variable 3-11 (gene/pseudogen 

24.99 0.006019354 CB RP1-128O3.5 24.91 0.000845487 CB RP11-554D14.3 24.51 0.043395953 CB MIR185 microRNA 185 24.08 0.046543212 CB RP11-544M22.3 23.4 0.006210424 CB RP11-120D12.2 23.16 0.00346671 CB RP11-481A20.4 22.91 0.023557449 CB IGKV3-11 immunoglobulin kappa variable 3-11 22.63 0.019304276 CB IGHV1-2 immunoglobulin heavy variable 1-2 22.09 0.012651023 CB TRBV11-1 T cell receptor beta variable 11-1 21.8 0.035979007 CB RP11-118B22.1 21.53 0.014367798 CB IGKV1-6 immunoglobulin kappa variable 1-6 19.5 0.017656956 CB IGKV3D-11 immunoglobulin kappa variable 3D-11 19.47 0.019058997 CB RP11-170L3.7 18.78 0.028374775 CB IGHV3-23 immunoglobulin heavy variable 3-23 17.5 0.02287369 CB IGKV1-12 immunoglobulin kappa variable 1-12 16.37 0.033794271 CB IL21 interleukin 21 16.05 0.024189646 CB IGHV1-24 immunoglobulin heavy variable 1-24 15.87 0.001953399 CB IGHV2-70 immunoglobulin heavy variable 2-70 15.8 0.001854517 CB RP11-118F2.3 15.48 0.010626103 CB RPS3AP33 ribosomal protein S3a pseudogene 33 15.32 0.012125647 CB TRBV7-3 T cell receptor beta variable 7-3 15.2 0.013029879 CB CXorf1 14.71 0.009648355 CB ADCY2 adenylate cyclase 2 (brain) 14.68 0.013827431 CB GPR25 G protein-coupled receptor 25 14.14 0.035978626 CB RP4-673D20.5 14.13 0.008612991 CB RPL36AP40 ribosomal protein L36a pseudogene 40 13.94 0.047090742 CB RP11-215P8.1 13.68 0.020435079 CB RP11-348B17.1 13.68 0.008070194 CB RP4-738P11.4 13.46 0.03745438 CB IGKV1D-12 immunoglobulin kappa variable 1D-12 13.21 0.04213223 CB RP11-386I23.1 13.2 0.002970807 CB IGKV4-1 immunoglobulin kappa variable 4-1 12.83 0.021040385 CB IGLV1-40 immunoglobulin lambda variable 1-40 12.37 0.045638568 CB GTSF1L gametocyte specific factor 1-like 12 0.017173685 CB IGKV1D-16 immunoglobulin kappa variable 1D-16 11.57 0.031078338 CB IGHV4-28 immunoglobulin heavy variable 4-28 11.31 0.048226887 CB GPR79 G protein-coupled receptor 79, pseudogene 11.3 0.033590863 CB IGLC6 immunoglobulin lambda constant 6 [Kern + Oz− marker, 

11.06 0.024790121 CB IGKV2-28 immunoglobulin kappa variable 2-28 10.81 0.01377845 CB CTD-2201E18.1 10.79 0.018497346 CB IGHV3-64 immunoglobulin heavy variable 3-64 10.53 0.047995343 CB AC009892.10 10.51 0.015181716 CB IGHG1 immunoglobulin heavy constant gamma 1 (G1m marke 

10.4 0.036386177 CB IGKV1-9 immunoglobulin kappa variable 1-9 10.34 0.028975593 CB RP11-500G10.4 10.13 0.021494609 CB IGKV2D-28 immunoglobulin kappa variable 2D-28 10.05 0.019434049 CB RP11-281P11.1 9.68 0.006912894 CB IGHV3-49 immunoglobulin heavy variable 3-49 9.68 0.022638595 CB CKMT1A creatine kinase, mitochondrial 1A 9.65 0.036386177 CB RP11-166B2.5 9.58 0.012166712 CB RP11-317B3.2 9.54 0.046077602 CB IGHJ4 immunoglobulin heavy joining 4 9.45 0.013184478 CB IGHGP immunoglobulin heavy constant gamma P (non-functio 

9.34 0.039288394 CB OR10G2 olfactory receptor, family 10, subfamily 6, member 2 9.09 0.012125647 CB IGHE immunoglobulin heavy constant epsilon 8.83 0.027654311 CB BMS1P5 BMS1 pseudogene 5 8.65 0.002970807 CB CST1 cystatin SN 8.61 0.034334741 CB IGHV1-69 immunoglobulin heavy variable 1-69 8.58 0.036189278 CB RP11-534L6.3 8.5 0.021641065 CB PPP1R14BP2 protein phosphatase 1, regulatory (inhibitor) subunit 1 

8.44 0.033515231 CB IGLV1-51 immunoglobulin lambda variable 1-51 8.42 0.046210752 CB GCNT1P3 glucosaminyl (N-acetyl) transferase 1, core 2 pseudoge 

8.28 0.049216823 CB RP11-151G12.2 8.26 0.015181716 CB RP4-620F22.3 7.94 0.041659897 CB CA14 carbonic anhydrase XIV 7.83 0.014371388 CB IGLV3-19 immunoglobulin lambda variable 3-19 7.8 0.049633437 CB SHD Src homology 2 domain containing transforming protei 

7.73 0.013031872 CB RP11-2A7A.3 7.58 0.028426013 CB IGHV4OR15-8 immunoglobulin heavy variable 4/OR15-8 (non-functio 

7.55 0.035978444 CB CKMT1B creatine kinase, mitochondrial 1B 7.53 0.045512017 CB IGKV1-5 immunoglobulin kappa variable 1-5 7.45 0.022360081 CB RP11-115A14.1 7.43 0.017845056 CB RP11-445O16.2 7.18 0.020838997 CB SLITRK2 SLIT and NTRK-like family, member 2 7.16 0.008070194 CB IGKJ5 immunoglobulin kappa joining 5 7.09 0.02643572 CB CTD-2235H24.2 7.08 0.030005872 CB IGKC immunoglobulin kappa constant 7.07 0.028688235 CB TTC24 tetratricopeptide repeat domain 24 7 0.04883796 CB IGHG3 immunoglobulin heavy constant gamma 3 (G3m marke 

7 0.017221389 CB LRRC26 leucine rich repeat containing 26 6.92 0.045085282 CB hsa-mir-220b 6.88 0.014969485 CB IGHJ3 immunoglobulin heavy joining 3 6.85 0.020251381 CB AC007050.17 6.83 0.040865625 CB RP11-33B1.3 6.75 0.045085282 CB IGKV3D-20 immunoglobulin kappa variable 3D-20 6.74 0.033794271 CB IGKJ5 immunoglobulin kappa joining 5 6.69 0.036339918 CB CHIT1 chitinase 1 (chitotriosidase) 6.68 0.017221389 CB IGKJ1 immunoglobulin kappa joining 1 6.65 0.02643572 CB CTD-2026G6.1 6.65 0.013184478 CB AC005041.17 6.57 0.039259375 CB IGLV7-43 immunoglobulin lambda variable 7-43 6.54 0.02199666 CB ADCYAP1 adenylate cyclase activating polypeptide 1 (pituitary) 6.5 0.043523654 CB TRBV3-1 T cell receptor beta variable 3-1 6.49 0.008690964 CB DUSP9 dual specificity phosphatase 9 6.49 0.015687171 CB PHGR1 proline/histidine/glycine-rich 1 6.48 0.009782763 CB TBL1Y transducin (beta)-like 1, Y-linked 6.42 0.03086908 CB IGLV3-1 immunoglobulin lambda variable 3-1 6.33 0.024742224 CB IGKJ2 immunoglobulin kappa joining 2 6.32 0.024814077 CB RP5-1198E17.1 6.24 0.048733769 CB AC096579.13 6.1 0.026864606 CB PAX5 paired box 5 6.08 0.04488914 CB AL928742.12 5.98 0.043395953 CB IGHM immunoglobulin heavy constant mu 5.97 0.049100171 CB DNM1P42 DNM 1 pseudogene 38 5.97 0.01373806 CB CPNE7 copine VII 5.96 0.018812935 CB IGHG2 immunoglobulin heavy constant gamma 2 (G2m marke 

5.91 0.02643572 CB RP11-1280I22.1 5.9 0.02678915 CB CCL18 chemokine (C-C motif) ligand 18 (pulmonary and activa 

5.87 0.02643572 CB IGKV3-20 immunoglobulin kappa variable 3-20 5.84 0.031363566 CB RP11-1166P10.5 5.83 0.020177433 CB RP11-17M16.1 5.77 0.026146007 CB TRAV6 T cell receptor alpha variable 6 5.73 0.027230317 CB IGJ 5.67 0.031092971 CB CD5L CD5 molecule-like 5.66 0.017111073 CB TRAV38-2DV8 T cell receptor alpha variable 38-2/delta variable 8 5.64 0.017111073 CB TRAV1-1 T cell receptor alpha variable 1-1 5.62 0.012652237 CB PAICSP3 phosphoribosylaminoimidazole carboxylase, phosphori 

5.61 0.022042996 CB RP11-367J7.3 5.52 0.024542839 CB IGLC1 immunoglobulin lambda constant 1 (Mcg marker) 5.41 0.024328524 CB SLC12A3 solute carrier family 12 (sodium/chloride transporter), 

5.4 0.021083625 CB IGLL5 immunoglobulin lambda-like polypeptide 5 5.37 0.022360081 CB TRBV11-2 T cell receptor beta variable 11-2 5.35 0.019899858 CB CTB-193M12.3 5.28 0.020059443 CB IGHV3-72 immunoglobulin heavy variable 3-72 5.2 0.014711317 CB HS3ST2 heparan sulfate (glucosamine) 3-O-sulfotransferase 2 5.19 0.015742933 CB FOXB1 forkhead box B1 5.06 0.047375038 CB IGHV3-7 immunoglobulin heavy variable 3-7 5.04 0.0422412 CB IGLJ1 immunoglobulin lambda joining 1 5.02 0.027138346 CB SUSD5 sushi domain containing 5 4.93 0.015742933 CB IRX2 iroquois homeobox 2 4.91 0.045478051 CB TRAV12-1 T cell receptor alpha variable 12-1 4.89 0.015921419 CB PTGDS prostaglandin D2 synthase 21 kDa (brain) 4.83 0.024328524 CB GOLGA7B golgin A7 family, member B 4.8 0.02052367 CB TCL1A T-cell leukemia/lymphoma 1A 4.8 0.047209651 CB RP11-731F5.2 4.74 0.031092971 CB IGHV3-53 immunoglobulin heavy variable 3-53 4.71 0.04213223 CB IGLV4-69 immunoglobulin lambda variable 4-69 4.68 0.014251282 CB SIGLEC8 sialic acid binding Ig-like lectin 8 4.66 0.003059735 CB IGHJ5 immunoglobulin heavy joining 5 4.65 0.047474072 CB RP11-798M19.3 4.63 0.032504427 CB RP11-615J4.4 4.62 0.02875596 CB RP11-236F9.5 4.62 0.012297912 CB FCRL3 Fc receptor-like 3 4.59 0.018812935 CB TRAV8-3 T cell receptor alpha variable 8-3 4.55 0.024375591 CB IL19 interleukin 19 4.5 0.026302018 CB ZBP1 Z-DNA binding protein 1 4.5 0.024814077 CB IGLV6-57 immunoglobulin lambda variable 6-57 4.49 0.046776361 CB AL109761.5 4.48 0.008747607 CB IGKV1-16 immunoglobulin kappa variable 1-16 4.45 0.017656956 CB FCRL1 Fc receptor-like 1 4.44 0.024742224 CB RP11-160A9.2 4.43 0.006059865 CB RP11-96D1.5 4.43 0.039680708 CB TUBB4A tubulin, beta 4A class IVa 4.42 0.02643572 CB IGHA1 immunoglobulin heavy constant alpha 1 4.41 0.024328524 CB RP11-46D6.1 4.38 0.024728355 CB FAM159A family with sequence similarity 159, member A 4.33 0.045512017 CB CD79A CD79a molecule, immunoglobulin-associated alpha 4.33 0.02643572 CB XXbac-B476C20.10 4.33 0.00890364 CB AC013444.1 4.32 0.009968933 CB CTD-3193O13.2 4.29 0.035096859 CB IGHJ6 immunoglobulin heavy joining 6 4.26 0.015703623 CB NSG1 neuron specific gene family member 1 4.25 0.045638568 CB UGT2B17 UDP glucuronosyltransferase 2 family, polypeptide B17 4.21 0.039234101 CB RUNX3 runt-related transcription factor 3 4.2 0.003059735 CB MS4A1 membrane-spanning 4-domains, subfamily A, member 

4.2 0.042370292 CB TRBV7-8 T cell receptor beta variable 7-8 4.15 0.003333637 CB C5orf38 4.11 0.038479039 CB AC098850.4 4.11 0.049100171 CB CD52 CD52 molecule 4.1 0.036386177 CB TRBV19 T cell receptor beta variable 19 4.1 0.014762458 CB RP11-752G15.3 4.09 0.007736506 CB ADAMDEC1 ADAM-like, decysin 1 4.04 0.026864606 CB HM13-IT1 HM13 intronic transcript 1 (non-protein coding) 4.02 0.008747607 CB FAIM3 Fas apoptotic inhibitory molecule 3 4 0.001257413 CB TRAV8-2 T cell receptor alpha variable 8-2 3.98 0.018415671 CB IGHD immunoglobulin heavy constant delta 3.97 0.019304276 CB CDH3 cadherin 3, type 1, P-cadherin (placental) 3.96 0.031092971 CB IGKV1D-13 immunoglobulin kappa variable 1D-13 3.93 0.041968771 CB TRBV6-5 T cell receptor beta variable 6-5 3.92 0.022828147 CB GAPDHP66 glyceraldehyde-3-phosphate dehydrogenase pseudoge 

3.91 0.028010999 CB AC110615.1 3.9 0.015372603 CB TRAV12-2 T cell receptor alpha variable 12-2 3.89 0.008789839 CB 3-Sep septin 3 3.89 0.028688235 CB RP11-444D3.1 3.83 0.026538797 CB IL12A interleukin 12A (natural killer cell stimulatory factor 1, 

3.8 0.000890132 CB RP11-166B2.3 3.8 0.016120921 CB POU2AF1 POU class 2 associating factor 1 3.74 0.02287369 CB AL137072.1 3.72 0.040458113 CB RP11-197M22.2 3.72 0.003591886 CB RP11-304L20.1 3.69 0.042281808 CB KLHDC7B kelch domain containing 7B 3.69 0.042370292 CB RP11-553K8.3 3.64 0.007203049 CB FCRL2 Fc receptor-like 2 3.62 0.033852011 CB IGKV3-15 immunoglobulin kappa variable 3-15 3.61 0.042339272 CB PLA2G2D phospholipase A2, group IID 3.59 0.011547361 CB TRBV20-1 T cell receptor beta variable 20-1 3.58 0.01262029 CB TRDV1 T cell receptor delta variable 1 3.58 0.044163971 CB IL24 interleukin 24 3.54 0.002180177 CB RASSF6 Ras association (RalGDS/AF-6) domain family member 

3.52 0.034369721 CB RP3-323N1.2 3.5 0.006129994 CB TRAV2 T cell receptor alpha variable 2 3.5 0.012569126 CB ZNF831 zinc finger protein 831 3.5 0.029054717 CB AC004906.3 3.48 0.033880884 CB Z97634.5 3.44 0.020435079 CB USP43 ubiquitin specific peptidase 43 3.42 0.036189278 CB IGHV1-3 immunoglobulin heavy variable 1-3 3.41 0.004030313 CB KCNIP3 Kv channel interacting protein 3, calsenilin 3.38 0.003059735 CB CUX2 cut-like homeobox 2 3.37 0.022828147 CB AC013264.2 3.36 0.025869773 CB ICOS inducible T-cell co-stimulator 3.36 0.02683945 CB TRBV29-1 T cell receptor beta variable 29-1 3.36 0.028975593 CB RP11-351I21.6 3.36 0.02643572 CB WNT10A wingless-type MMTV integration site family, member 1 

3.35 0.039148946 CB FCRLA Fc receptor-like A 3.34 0.033656613 CB TIGIT T cell immunoreceptor with Ig and ITIM domains 3.33 0.033656613 CB AC009499.1 3.32 0.03076835 CB TRBV4-1 T cell receptor beta variable 4-1 3.28 0.041968771 CB HLA-DQA1 major histocompatiblity complex, class II, DQ alpha 1 3.26 0.033656613 CB DNTT DNA nucleotidylexotransferase 3.25 0.016753819 CB GNG4 guanine nucleotide binding protein (G protein), gamma 

3.24 0.029028339 CB RP11-641C17.4 3.23 0.016475123 CB CD72 CD72 molecule 3.23 0.018812935 CB ST8SIA6 ST8 alpha-N-acetyl-neuraminide alpha-2,8-siafyltransfe 

3.23 0.042370292 CB KIAA0125 KIAA0125 3.23 0.033698056 CB PTCRA pre T-cell antigen receptor alpha 3.22 0.026404029 CB UBASH3A ubiquitin associated and SH3 domain containing A 3.22 0.016408594 CB PYHIN1 pyrin and HIN domain family, member 1 3.19 0.011925792 CB EOMES eomesodermin 3.19 0.001902564 CB CD6 CD6 molecule 3.18 0.011925792 CB RP11-74K11.1 3.18 0.04213223 CB LILRA4 leukocyte immunoglobulin-like receptor, subfamily A ( 

3.18 0.015742933 CB CD3G CD3g molecule, gamma (CD3-TCR complex) 3.17 0.010595239 CB TRAV3 T cell receptor alpha variable 3 (gene/pseudogene) 3.17 0.04488914 CB OR6S1 olfactory receptor, family 6, subfamily S, member 1 3.16 0.033574388 CB IGKV3D-15 immunoglobulin kappa variable 3D-15 (gene/pseudoge 

3.15 0.02683945 CB S1PR4 sphingosine-1-phosphate receptor 4 3.14 0.04883796 CB MNX1 motor neuron and pancreas homeobox 1 3.12 0.037825665 CB LY9 lymphocyte antigen 9 3.1 0.021105252 CB RP11-481A20.10 3.08 0.023509294 CB RP11-80A15.1 3.08 0.01692508 CB RP1-127D3.4 3.06 0.012666399 CB RP11-290F20.3 3.06 0.011925792 CB AL139819.1 3.05 0.013811098 CB ACTL8 actin-like 8 3.04 0.0100951 CB ZBED2 zinc finger, BED-type containing 2 3.03 0.004030313 CB ITK IL2-inducible T-cell kinase 3.03 0.049100171 CB TRAV1-2 T cell receptor alpha variable 1-2 3.02 0.009442924 CB SLAMF6 SLAM family member 6 3.01 0.010840451 CB RPSAP53 ribosomal protein SA pseudogene 53 3.01 0.028688235 CB RP11-481A20.11 2.99 0.009241778 CB IDO1 indoleamine 2,3-dioxygenase 1 2.99 0.021105252 CB RP11-195C7.3 2.98 0.029602879 CB HSH2D hematopoietic SH2 domain containing 2.98 0.028975593 CB AC002306.1 2.97 0.021494609 CB RP11-379H8.1 2.96 0.036500639 CB CRYM crystallin, mu 2.96 0.045478051 CB CXorf57 2.96 0.017221389 CB KRT27 keratin 27 2.95 0.011193228 CB SNRPFP1 small nuclear ribonucleoprotein polypeptide F pseudog 

2.95 0.047209651 CB IGLV2-11 immunoglobulin lambda variable 2-11 2.95 0.028975593 CB RP11-293F5.4 2.9 0.030369085 CB SPOCK2 sparc/osteonectin, cwcv and kazal-like domains proteo 

2.9 0.028688235 CB C11orf41 2.9 0.02052367 CB CD7 CD7 molecule 2.9 0.036386177 CB FSD1 fibronectin type III and SPRY domain containing 1 2.9 0.031391184 CB TMEM191A transmembrane protein 191A (pseudogene) 2.9 0.026864606 CB RP11-292F22.3 2.89 0.032737245 CB RAB19 RAB19, member RAS oncogene family 2.88 0.033351877 CB PRF1 perforin 1 (pore forming protein) 2.88 0.015742933 CB RP11-332O19.3 2.85 0.007014254 CB CTC-422A18.2 2.84 0.040365068 CB NR4A3 nuclear receptor subfamily 4, group A, member 3 2.84 0.004785714 CB CD3D CD3d molecule, delta (CD3-TCR complex) 2.84 0.014371388 CB SCML1 sex comb on midleg-like 1 (Drosophila) 2.84 0.031092971 CB THEMIS thymocyte selection associated 2.83 0.045478051 CB HSD11B1 hydroxysteroid (11-beta) dehydrogenase 1 2.81 0.028688235 CB IL28RA interferon, lambda receptor 1 2.8 0.010595239 CB GNLY granulysin 2.8 0.014371388 CB RP11-429J17.6 2.8 0.014371388 CB LCK lymphocyte-specific protein tyrosine kinase 2.79 0.015079112 CB RPL5P32 ribosomal protein L5 pseudogene 32 2.78 0.019540488 CB AC023490.1 2.78 0.013100955 CB RP11-564A8.4 2.77 0.000583885 CB RP11-220D10.1 2.77 0.017559073 CB TNFRSF11B tumor necrosis factor receptor superfamily, member 1 

2.75 0.042339272 CB ATP1A3 ATPase, Na+/K+ transporting, alpha 3 polypeptide 2.73 0.024328524 CB IKZF3 IKAROS family zinc finger 3 (Aiolos) 2.72 0.014371388 CB C16orf54 2.7 0.029054717 CB AC008984.2 2.7 0.004072591 CB CXCL13 chemokine (C-X-C motif) ligand 13 2.69 0.019434049 CB RP11-599J14.2 2.67 0.039288394 CB TRAV5 T cell receptor alpha variable 5 2.67 0.033575171 CB RP11-566K11.2 2.67 0.035185369 CB CD96 CD96 molecule 2.66 0.042339272 CB C8orf80 2.66 0.036500639 CB TNFRSF13B tumor necrosis factor receptor super-family, member 1 

2.65 0.04352477 CB TRAV13-1 T cell receptor alpha variable 13-1 2.64 0.024662434 CB EIF4BP9 eukaryotic translation initiation factor 48 pseudogene 

2.64 0.007991506 CB PTPRCAP protein tyrosine phosphatase, receptor type, C-associa 

2.62 0.02052367 CB SLC24A4 solute carrier family 24 (sodium/potassium/calcium ex 

2.62 0.028688235 CB GZMH granzyme H (cathepsin G-like 2, protein h-CCPX) 2.61 0.045512017 CB TBX21 T-box 21 2.61 0.021040385 CB SLC22A18AS solute carrier family 22 (organic cation transporter), m 

2.59 0.036530778 CB LINC00426 long intergenic non-protein coding RNA 426 2.59 0.009381276 CB HSBP1L1 heat shock factor binding protein 1-like 1 2.58 0.001681771 CB TRAC T cell receptor alpha constant 2.57 0.013100955 CB MTFP1 mitochondrial fission process 1 2.57 0.00657893 CB 1-Sep septin 1 2.55 0.039288394 CB IL6R interleukin 6 receptor 2.54 0.049100171 CB RP11-61I13.2 2.54 0.017952081 CB CATSPERB catsper channel auxiliary subunit beta 2.53 0.022360081 CB LAG3 lymphocyte-activation gene 3 2.52 0.028688235 CB LTB lymphotoxin beta (TNF superfamily, member 3) 2.51 0.036386177 CB GZMB granzyme B (granzyme 2, cytotoxic T-lymphocyte-asso 

2.51 0.026688235 CB TRBV4-2 T cell receptor beta variable 4-2 2.49 0.048226887 CB C14orf182 2.49 0.009675088 CB HS3ST3B1 heparan sulfate (glucosamine) 3-O-sulfotransferase 3B 

2.49 0.045512017 CB CTD-2562J17.3 2.48 0.002755485 CB RP11-630I5.1 2.46 0.047209651 CB BEND4 BEN domain containing 4 2.46 0.003304376 CB IL12RB1 interleukin 12 receptor, beta 1 2.45 0.045638568 CB KLHL6 kelch-like family member 6 2.44 0.049100171 CB RP11-126K1.8 2.43 0.021734161 CB PARP15 poly (ADP-ribose) polymerase family, member 15 2.43 0.02643572 CB RP13-554M15.6 2.43 0.020709572 CB TMEM238 transmembrane protein 238 2.43 0.011925792 CB AC104698.1 2.41 0.026170063 CB FASLG Fas ligand (TNF superfamily, member 6) 2.4 0.028975593 CB GYLTL1B glycosyltransferase-like 1B 2.39 0.029054717 CB IL29 interferon, lambda 1 2.38 0.030404894 CB GZMK granzyme K (granzyme 3; tryptase ▮) 2.37 0.024742224 CB FHOD3 formin homology 2 domain containing 3 2.37 0.042370292 CB PRUNE2 prune homolog 2 (Drosophila) 2.36 0.042370292 CB FXYD5 FXYD domain containing ion transport regulator 5 2.35 0.002724323 CB CTLA4 cytotoxic T-lymphocyte-associated protein 4 2.34 0.024814077 CB ATP13A4-AS1 ATP13A4 antisense RNA 1 2.34 0.015249492 CB RP11-44K6.4 2.34 0.036500639 CB PFKP phosphofructokinase, platelet 2.34 0.011925792 CB TRAV8-4 T cell receptor alpha variable 8-4 2.34 0.02857165 CB RP11-1094M14.3 2.34 0.049100171 CB ZMYND12 zinc finger, MYND-type containing 12 2.33 0.024328524 CB TRBC2 T cell receptor beta constant 2 2.33 0.011925792 CB RP11-1396O13.20 2.32 0.024328524 CB TRBV5-5 T cell receptor beta variable 5-5 2.32 0.049758592 CB TRAT1 T cell receptor associated transmembrane adaptor 1 2.31 0.045478051 CB CHAC1 ChaC, cation transport regulator homolog 1 (E. coli) 2.31 0.011925792 CB SLC1A4 solute carrier famiy 1 (glutamate/neutral amino acid t 

2.3 0.013100955 CB RPS3AP34 ribosomal protein S3a pseudogene 34 2.3 0.018812935 CB RP11-982M15.6 2.3 0.036386177 CB JAKMIP1 jan us kinase and microtubule interacting protein 1 2.29 0.033852011 CB CPEB1 cytoplasmic polyadenylation element binding protein 1 2.29 0.039288394 CB AC104820.2 2.28 0.002764257 CB KCNMA1 potassium large conductance calcium-activated channe 2.28 0.022360081 CB RP11-93B14.6 2.28 0.022437406 CB NCF1B neutrophil cytosolic factor 1B pseudogene 2.27 0.049100171 CB HLF hepatic leukemia factor 2.27 0.049100171 CB RPS6KA1 ribosomal protein S6 kinase, 90 kDa, polypeptide 1 2.26 0.013100955 CB RP13-735L24.1 2.26 0.03877208 CB TMEM108 transmembrane protein 108 2.25 0.045638568 CB RP11-982M15.8 2.25 0.049369302 CB IGFLR1 IGF-like family receptor 1 2.24 0.036386177 CB TNIP3 TNIFAIP3 interacting protein 3 2.23 0.031391184 CB RP11-443A13.3 2.23 0.015742933 CB TRGV7 T cell receptor gamma variable 7 (pseudogene) 2.22 0.011590706 CB OIT3 ancoprotein induced transcript 3 2.22 0.036500639 CB SLA2 Src-like-adaptor 2 2.22 0.018812935 CB ZNF683 zinc finger protein 683 2.21 0.045478051 CB SAMD5 sterile alpha motif domain containing 5 2.21 0.029054717 CB GPR174 G protein-coupled receptor 174 2.21 0.031391184 CB SASH3 SAM and SH3 domain containing 3 2.21 0.022360081 CB LAX1 lymphocyte transmembrane adaptor 1 2.2 0.033656613 CB KCNAB2 potassium voltage-gated channel, shaker related subfa 

2.19 0.003430441 CB HIST1H2BG histone cluster 1, H2bg 2.19 0.039288394 CB BIK BCL2-interacting killer (apoptosis-inducing) 2.19 0.015079112 CB CD2 CD2 molecule 2.18 0.033656613 CB RP11-10G12.1 2.17 0.008391308 CB FTH1P24 ferritin, heavy polypeptide 1 pseudogene 24 2.17 0.041434796 CB PLP2 proteolipid protein 2 (colonic epithelium-enriched) 2.17 0.003839527 CB SLC34A1 solute carrier family 34 (type II sodium/phosphate cont 

2.16 0.041434796 CB RP11-771F20.1 2.16 0.031092971 CB IFITM5 interferon induced transmembrane protein 5 2.15 0.036189278 CB RP11-390B4.3 2.13 0.004290131 CB CXCR3 chemokine (C-X-C motif) receptor 3 2.13 0.039288394 CB TRGC1 T cell receptor gamma constant 1 2.12 0.039316473 CB CD3E CD3e molecule, epsilon (CD3-TCR complex) 2.12 0.012666399 CB SIT1 signaling threshold regulating transmembrane adaptor 2.11 0.033852011 CB NKG7 natural killer cell granule protein 7 2.11 0.024328524 CB C1orf51 2.1 0.028588235 CB ABCD2 ATP binding cassette, sub-family D (ALD), member 2 2.1 0.028688235 CB TNIK TRAF2 and NCK interacting kinase 2.09 0.045638568 CB DNAJC6 DnaJ (Hsp40) homolog, subfamily C, member 6 2.08 0.036386177 CB SLCO4A1 solute carrier organic anion transporter family, membe 

2.08 0.031092971 CB HSD3B7 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and st 

2.07 0.004290131 CB CR2 complement component (3d/Epstein Barr virus) recept 

2.06 0.042339272 CB TC2N tandem C2 domains, nuclear 2.06 0.045638568 CB IL12RB2 interleukin 12 receptor, beta 2 2.05 0.028688235 CB RGS14 regulator of G-protein signaling 14 2.05 0.005329798 CB CLEC19A C-type lectin domain family 19, member A 2.04 0.041659897 CB MYO1G myosin IG 2.03 0.049100171 CB RHBDL1 rhomboid, veinlet-like 1 (Drosophia) 2.03 0.024328524 CB CD19 CD19 molecule 2.03 0.028688235 CB TJP3 tight junction protein 3 2.03 0.021083625 CB PIK3CD phosphatidylinositol-4,5-bisphosphate 3-kinase, catalyt 

2.02 0.022360081 CB DHRS9 dehydrogenase/reductase (SDR family) member 9 2.02 0.008917729 CB RP3-453I5.2 2.02 0.031835936 CB ITGAL integrin, alpha L (antigen CD11A (p180), lymphocyte fu 

2.02 0.024328524 CB NLRC5 NLR family, CARD domain containing 5 2.02 0.009839457 CB LPIN3 lipin 3 2.02 0.036386177 CB NLGN4Y neuroligin 4, Y-linked 2.02 0.036386177 CB DTHD1 death domain containing 1 2.01 0.039347886 CB RP11-351I21.7 2.01 0.033656613 CB FOXH1 forkhead box H1 2.01 0.038385003 CB ZNF296 zinc finger protein 296 2.01 0.039288394 CB

indicates data missing or illegible when filed

TABLE 3 Genes enriched in TCGA Xq28-CGA-high/low expression samples Gene Gene_Name Fold_Change P-value Group ?|100133144 2.57 4.18E−06 Xq28-CGA high ?|100134869 2.59 7.35E−09 Xq28-CGA high ?|340602 2.1 2.38E−05 Xq28-CGA high ?|391343 3.38 2.94E−15 Xq28-CGA high AACSL|729522 acetoacetyl-CoA synthetase pseudogene 1 5.79 1.38E−14 Xq28-CGA high ABCA8|10351 ATP-binding cassette, sub-family A (ABC1), mem

11.7 2.59E−05 Xq28-CGA high ABHD1|84696 abhydrolase domain containing 1 2.2 9.03E−07 Xq28-CGA high ACCN4|55515 acid-sensing (proton-gated) ion channel family m

2.68 3.92E−05 Xq28-CGA high ACOT11|26027 acyl-CoA thioesterase 11 2.01 9.52E−07 Xq28-CGA high ACSM3|6296 acyl-CoA synthetase medium-chain family memb

2.11 1.45E−04 Xq28-CGA high ADAM21P1|145241 ADAM metallopeptidase domain 21 pseudogene

2.04 1.45E−06 Xq28-CGA high ADAM21|8747 ADAM metallopeptidase domain 21 2.16 7.13E−05 Xq28-CGA high ADAMTS20|80070 ADAM metallopeptidase with thrombospondin t

8.83 5.40E−18 Xq28-CGA high ADAMTS3|9508 ADAM metallopeptidase with thrombospondin t

3.28 8.96E−05 Xq28-CGA high AGBL4|84871 ATP/GTP binding protein-like 4 2.86 5.45E−07 Xq28-CGA high AKAP6|9472 A kinase (PRKA) anchor protein 6 5.2 1.25E−09 Xq28-CGA high ALDH1L1|10840 aldehyde dehydrogenase 1 family, member L1 4.51 1.49E−05 Xq28-CGA high ALDH8A1|64577 aldehyde dehydrogenase 8 family, member A1 2.29 8.54E−09 Xq28-CGA high ANGPT1|284 angiopoietin 1 16.65 7.33E−21 Xq28-CGA high ANKFN1|162282 ankyrin-repeat and fibronectin type III domain c

3.97 2.53E−06 Xq28-CGA high ANKRD20A3|441425 ankyrin repeat domain 20 family, member A3 2.03 2.97E−05 Xq28-CGA high ANKRD20A4|728747 ankyrin repeat domain 20 family, member A4 2.02 4.49E−05 Xq28-CGA high ANKRD20B|729171 ankyrin repeat domain 20 family, member A8, p

3.12 1.46E−13 Xq28-CGA high ANKRD43|134548 ankyrin repeat domain family member A 2.23 6.52E−07 Xq28-CGA high ANKRD45|339416 ankyrin repeat domain 45 8.13 7.90E−12 Xq28-CGA high ANKRD7|56311 ankyrin repeat domain 7 2.62 2.73E−06 Xq28-CGA high ANO3|63982 anoctamin 3 10.84 3.30E−15 Xq28-CGA high ANO4|121601 anoctamin 4 6.62 7.25E−07 Xq28-CGA high ANO5|203859 anoctamin 5 6.36 6.54E−05 Xq28-CGA high ARHGEF35|445328 Rho guanine nucleotide exchange factor (GEF) 3

3.74 5.02E−07 Xq28-CGA high ARHGEF5|7984 Rho guanine nucleotide exchange factor (GEF) 5 2.61 1.31E−04 Xq28-CGA high ART3|419 ADP-ribosyltransferase 3 3.07 1.68E−05 Xq28-CGA high ASB4|51666 ankyrin repeat and SOCS box containing 4 9.37 2.34E−10 Xq28-CGA high ASCL1|429 achaete-scute family bHLH transcription factor 1

6.46 3.94E−10 Xq28-CGA high ATP1B1|481 ATPase, Na+/K+ transporting, beta 1 polypeptide

2.33 2.89E−06 Xq28-CGA high ATP1B2|482 ATPase, Na+/K+ transporting, beta 2 polypeptide

6.39 4.48E−07 Xq28-CGA high AURKAPS1|6791 aurora kinase A pseudogene 1 2.27 9.37E−18 Xq28-CGA high AZGP1|563 alpha-2-glycoprotein 1, zinc-binding 3.89 2.93E−09 Xq28-CGA high B3GALNT1|8706 beta-1,3-N-acetylgalactosaminyltransferase 1 (g

3.07 9.52E−07 Xq28-CGA high BAAT|570 bile acid CoA: amino add N-acyltransferase (glyc

4.88 1.10E−04 Xq28-CGA high BAGE2|85319 B melanoma antigen family, member 2 6.61 6.56E−19 Xq28-CGA high BAGE|574 B melanoma antigen 322.69 8.19E−30 Xq28-CGA high BDKRB1|623 bradykinin receptor B1 2.02 4.21E−06 Xq28-CGA high C10orf62|414157 2.32 1.91E−07 Xq28-CGA high C11orf9|745 3.02 7.92E−07 Xq28-CGA high C12orf56|115749 12.21 2.93E−08 Xq28-CGA high C17orf47|284083 2.01 5.46E−06 Xq28-CGA high C17orf57|124989 2.69 1.88E−09 Xq28-CGA high C18orf2|56651 135.15 1.52E−22 Xq28-CGA high C1QTNF3|114899 C1q and tumor necrosis factor related protein 3 3.69 6.53E−06 Xq28-CGA high C1orf114|57821 9.23 8.34E−11 Xq28-CGA high C1orf175|374977 2.41 4.24E−06 Xq28-CGA high C1orf88|128344 2.19 5.98E−05 Xq28-CGA high C21orf29|54084 2.29 2.18E−07 Xq28-CGA high C21orf90|114043 10.16 2.71E−11 Xq28-CGA high C22orf34|348645 6.07 2.01E−12 Xq28-CGA high C2orf61|285051 2.72 3.12E−05 Xq28-CGA high C2orf66|401027 3.05 2.73E−07 Xq28-CGA high C3orf20|84077 2.16 5.04E−05 Xq28-CGA high C3orf30|152405 6.01 1.77E−13 Xq28-CGA high C3orf50|93556 7.19 1.32E−04 Xq28-CGA high C3orf66|677779 10.47 7.19E−07 Xq28-CGA high C4orf19|55286 4.83 1.11E−07 Xq28-CGA high C4orf37|285555 2.87 1.39E−04 Xq28-CGA high C4orf6|10141 3.81 3.52E−05 Xq28-CGA high C5orf58|133874 3.33 4.42E−07 Xq28-CGA high C6orf164|63914 2.09 4.98E−06 Xq28-CGA high C7orf51|222950 2.06 9.21E−06 Xq28-CGA high C7orf71|285941 2.42 5.51E−05 Xq28-CGA high C8orf85|441376 4.73 2.02E−07 Xq28-CGA high CA6|765 carbonic anhydrase VI 8.97 7.57E−05 Xq28-CGA high CABP4|57010 calcium tending protein 4 2.09 2.10E−05 Xq28-CGA high CABYR|26256 calcium binding tyrosine-(Y)-phosphorylation reg

2.12 9.54E−06 Xq28-CGA high CADM4|199731 cell adhesion molecule 4 2.43 2.24E−07 Xq28-CGA high CALCB|797 calcitonin-related polypeptide beta 2.36 1.45E−04 Xq28-CGA high CAND2|23066 cullin-associated and neddylation-dissociated 2

2.58 2.69E−05 Xq28-CGA high CASP12|120329 caspase 12 (gene/pseudogene) 2.92 1.13E−04 Xq28-CGA high CCDC136|64753 coiled-coil domain containing 136 3.39 3.18E−10 Xq28-CGA high CCDC144A|9720 coiled-coil domain containing 144A 2.57 4.08E−07 Xq28-CGA high CCDC144B|284047 coiled-coil domain containing 144B (pseudogene

2.21 1.80E−08 Xq28-CGA high CCDC144C|348254 coiled-coil domain containing 144C, pseudogene

2.08 5.83E−07 Xq28-CGA high CCDC160|347475 coiled-coil domain containing 160 5.56 2.95E−07 Xq28-CGA high CCDC46|201134 centrosomal protein 112 kDa 2.21 2.31E−05 Xq28-CGA high CCR10|2826 chemokine (C-C motif) receptor 10 2.59 6.20E−05 Xq28-CGA high CDH12|1010 cadherin 12, type 2 (N-cadherin 2) 2.06 1.18E−10 Xq28-CGA high CDH18|1016 cadherin 18, type 2 2.26 1.43E−08 Xq28-CGA high CDK14|5218 cyclin-dependent kinase 14 2.15 2.69E−05 Xq28-CGA high CDK6|1021 cyclin-dependent kinase 6 2.03 3.37E−09 Xq28-CGA high CFHR4|10877 complement factor H-related 4 3.93 3.25E−15 Xq28-CGA high CFI|3426 complement factor I 2.32 6.77E−06 Xq28-CGA high CHML|1122 choroideremia-like (Rab escort protein 2) 2.29 8.66E−10 Xq28-CGA high CHRM3|1131 cholinergic receptor, muscarinic 3 6.32 8.83E−09 Xq28-CGA high CLEC18B|497190 C-type lectin domain family 18, member B 2.8 2.48E−07 Xq28-CGA high CLEC18C|283971 C-type lectin domain family 18, member C 3.29 2.57E−06 Xq28-CGA high CLEC2L|154790 C-type lectin domain family 2, member L 4.49 5.06E−10 Xq28-CGA high CLGN|1047 calmegin 2.63 1.48E−04 Xq28-CGA high CMTM8|152189 CKLF-like MARVEL transmembrane domain cont

2.03 2.30E−06 Xq28-CGA high CNDP1|84735 carnosine dipeptidase 1 (metallopeptidase M20 10.44 2.04E−07 Xq28-CGA high CNR1|1268 cannabinoid receptor 1 (brain) 5.5 1.89E−08 Xq28-CGA high COL11A2|1302 collagen, type XI, alpha 2 4.71 4.25E−06 Xq28-CGA high COL25A1|84570 collagen, type XXV, alpha 1 3.06 2.67E−05 Xq28-CGA high COL28A1|340267 collagen, type XXVIII, alpha 1 2.41 6.36E−07 Xq28-CGA high COX6A2|1339 cytochrome c oxidase subunit VIa polypeptide 2 24.16 9.07E−06 Xq28-CGA high CPS1|1373 carbamoyl-phosphate synthase 1, mitochondrial

2.14 5.82E−05 Xq28-CGA high CPT1C|126129 carnitine palmitoyltransferase 1C 2.45 5.38E−08 Xq28-CGA high CSAG1|158511 chondrosarcoma associated gene 1 1195.25 2.66E−40 Xq28-CGA high CSAG2|728461 CSAG family, member 2 2834.71 1.71E−44 Xq28-CGA high CSAG3|389903 CSAG family, member 3 907.95 2.54E−40 Xq28-CGA high CSMD1|64478 CUB and Sushi multiple domains 1 65.06 9.87E−23 Xq28-CGA high CSNK1A1P|161635 casein kinase 1, alpha 1 pseudogene 1 2.79 1.12E−04 Xq28-CGA high CTAG1B|1485 cancer/testis antigen 1B 2124.92 2.20E−23 Xq28-CGA high CTAG2|30848 cancer/testis antigen 2 3883.48 5.49E−22 Xq28-CGA high CTAGE4|100128553 CTAGE family, member 4 3.87 4.57E−08 Xq28-CGA high CTAGE6|340307 CTAGE family, member 6 2.55 1.66E−07 Xq28-CGA high CTAGE9|643854 CTAGE family, member 9 4.12 1.72E−08 Xq28-CGA high CUZD1|50624 CUB and zona pellucida-like domains 1 2.51 3.82E−07 Xq28-CGA high CXorf42|158801 2.95 1.11E−04 Xq28-CGA high CXorf48|54967 9.38 5.16E−17 Xq28-CGA high CXorf49B|100132994 2.41 1.66E−09 Xq28-CGA high CYP26A1|1592 cytochrome P450, family 26, subfamily A, polype

3.95 4.44E−08 Xq28-CGA high CYP2J2|1573 cytochrome P450, family 2, subfamily J, polypep

6.31 4.44E−11 Xq28-CGA high DCAF4L1|285429 DDB1 and CUL4 associated factor 4-like 1 2.41 2.05E−10 Xq28-CGA high DCAF4L2|138009 DDB1 and CUL4 associated factor 4-like 2 2.39 5.69E−07 Xq28-CGA high DCAF8L2|347442 DDB1 and CUL4 associated factor 8-like 2 3.37 1.15E−08 Xq28-CGA high DDIT4L|115265 DNA-damage-inducible transcript 4-like 2.07 9.75E−05 Xq28-CGA high DDO|8528 D-aspartate oxidase 6.08 6.90E−08 Xq28-CGA high DDX25|29118 DEAD (Asp-Glu-Ala-Asp) box helicase 25 3.43 3.83E−06 Xq28-CGA high DEPDC1|55635 DEP domain containing 1 2.07 8.23E−07 Xq28-CGA high DHDPSL|112817 4-hydroxy-2-oxoglutarate aldolase 1 2.24 3.77E−06 Xq28-CGA high DHRS2|10202 dehydrogenase/reductase (SDR family) member 3.49 1.53E−05 Xq28-CGA high DLX2|1746 distal-less homeobox 2 2.35 1.54E−05 Xq28-CGA high DMP1|1758 dentin matrix acidic phosphoprotein 1 2.14 2.47E−06 Xq28-CGA high DNAH2|146754 dynein, axonemal, heavy chain 2 9.72 3.37E−08 Xq28-CGA high DNAH3|55567 dynein, axonemal, heavy chain 3 2.36 5.81E−10 Xq28-CGA high DNAH7|56171 dynein, axonemal, heavy chain 7 2.16 2.09E−05 Xq28-CGA high DNAJC22|79962 DnaJ (Hsp40) homolog, subfamily C, member 22 2.03 3.99E−06 Xq28-CGA high DNALI1|7802 dynein, axonemal, light intermediate chain 1 8.88 1.18E−07 Xq28-CGA high DPY19L2P1|554236 DPY19L2 pseudogene 1 2.35 0.000128592 Xq28-CGA high DSCR10|259234 Down syndrome critical region gene 10 (non-pro

4.72 2.66E−16 Xq28-CGA high DSCR4|10281 Down syndrome critical region gene 4 109.57 9.21E−27 Xq28-CGA high DSCR8|84677 Down syndrome critical region gene 8 2470.84 5.96E−28 Xq28-CGA high E2F8|79733 E2F transcription factor 8 2.29 3.82E−09 Xq28-CGA high EFHC2|80258 EF-hand domain (C-terminal) containing 2 4.41 7.66E−06 Xq28-CGA high EGF|1950 epidermal growth factor 3.74 1.76E−07 Xq28-CGA high ELAVL4|1996 ELAV like neuron-specific RNA binding protein 4 2.26 4.54E−06 Xq28-CGA high ELOVL2|54898 ELOVL fatty add elongase 2 3.7 3.24E−08 Xq28-CGA high ENPP4|22875 ectonucleotide pyrophosphatase/phosphodieste

3.06 4.19E−06 Xq28-CGA high ENPP5|59084 ectonucleotide pyrophosphatase/phosphodieste

4.98 1.50E−06 Xq28-CGA high EPHX4|253152 epoxide hydrolase 4 3.73 1.05E−04 Xq28-CGA high ERC2|26059 ELKS/RAB6-interacting/CAST family member 2 2.47 7.71E−07 Xq28-CGA high ERRFI1|54206 ERBB receptor feed back inhibitor 1 2.05 7.88E−08 Xq28-CGA high ESRRG|2104 estrogen-related receptor gamma 4.89 1.36E−04 Xq28-CGA high EYA1|2138 eyes absent homolog 1 (Drosophila) 40.69 6.57E−09 Xq28-CGA high F5|2153 coagulation factor V (proaccelerin, labile factor) 2.39 3.01E−05 Xq28-CGA high FABP6|2172 fatty acid binding protein 6, ileal 15.12 6.38E−07 Xq28-CGA high FABP7|2173 fatty acid binding protein 7, brain 5.61 4.79E−05 Xq28-CGA high FAM106A|80039 family with sequence similarity 106, member A 2.91 8.62E−05 Xq28-CGA high FAM106C|100129396 family with sequence similarity 106, member C,

2.62 4.24E−07 Xq28-CGA high FAM133A|286499 family with sequence similarity 133, member A 85.36 1.01E−24 Xq28-CGA high FAM181B|220382 family with sequence similarity 181, member B 2.58 5.11E−05 Xq28-CGA high FAM196B|100131897 family with sequence similarity 196, member B 3.67 1.59E−05 Xq28-CGA high FAM46D|169966 family with sequence similarity 46, member D 3.06 4.07E−05 Xq28-CGA high FAM81B|153643 family with sequence similarity 81, member B 2.77 5.78E−05 Xq28-CGA high FBXL13|222235 F-box and leucine-rich repeat protein 13 2.47 2.05E−11 Xq28-CGA high FER1L4|80307 fer-1-like 4 (C. elegans), pseudogene 2.43 7.52E−06 Xq28-CGA high FGF2|2247 fibroblast growth factor 2 (basic) 3.96 1.07E−06 Xq28-CGA high FHAD1|114827 forkhead-associated (FHA) phosphopeptide bind

4.6 2.36E−09 Xq28-CGA high FIGF|2277 c-fos induced growth factor (vascular endothelia

2.69 2.20E−06 Xq28-CGA high FKBP1B|2281 FK506 binding protein 1B, 12.6 kDa 2.35 1.77E−07 Xq28-CGA high FLI36000|284124 uncharacterized FLI36000 21.56 3.27E−13 Xq28-CGA high FLI44606|401207 2.53 1.53E−06 Xq28-CGA high FMNL2|114793 formin-like 2 2.09 1.37E−07 Xq28-CGA high FOXA3|3171 forkhead box A3 2.6 4.37E−05 Xq28-CGA high FOXR2|139628 forkhead box R2 2.42 1.05E−10 Xq28-CGA high FRAS1|80144 Fraser syndrome 1 3.4 8.26E−05 Xq28-CGA high G6PC2|57818 glucose-6-phosphatase, catalytic, 2 2.57 1.53E−04 Xq28-CGA high GABRA3|2556 gamma-aminobutyric acid (GABA) A receptor, al

530.61 4.59E−39 Xq28-CGA high GABRB1|2560 gamma-aminobutyric acid (GABA) A receptor, be

3.14 1.41E−07 Xq28-CGA high GABRG2|2566 gamma-aminobutyric acid (GABA) A receptor, ga

7.02 5.68E−19 Xq28-CGA high GABRP|2568 gamma-aminobutyric acid (GABA) A receptor, pi

3.95 3.91E−06 Xq28-CGA high GABRQ|55879 gamma-aminobutyric acid (GABA) A receptor, th

9.7 2.72E−17 Xq28-CGA high GAGE12D|100132399 G antigen 12D 399.62 1.14E−17 Xq28-CGA high GAGE12J|729396 G antigen 12J 45.61 1.67E−18 Xq28-CGA high GAGE1|2543 G antigen 1 45.46 1.61E−16 Xq28-CGA high GAGE2A|729447 G antigen 2A 21.71 4.92E−13 Xq28-CGA high GAGE2D|729408 G antigen 2D 209.41 7.37E−17 Xq28-CGA high GAGE4|2576 G antigen 4 300.81 1.27E−18 Xq28-CGA high GAGE8|100101629 G antigen 8 12.62 5.69E−13 Xq28-CGA high GALNT8|26290 polypeptide N-acetylgalactosaminyltransferase 8

2.32 1.82E−08 Xq28-CGA high GAP43|2596 growth associated protein 43 4.67 1.31E−06 Xq28-CGA high GAS2|2620 growth arrest-specific 2 2.16 3.79E−06 Xq28-CGA high GBA3|57733 glucosidase, beta, acid 3 (gene/pseudogene) 4.36 1.08E−06 Xq28-CGA high GDNF|2668 glial cell derived neurotrophic factor 6.24 7.41E−07 Xq28-CGA high GJC3|349149 gap junction protein, gamma 3, 30.2 kDa 2.03 2.74E−05 Xq28-CGA high GLB1L|79411 galactosidase, beta 1-like 2.76 2.05E−07 Xq28-CGA high GLRB|2743 glycine receptor, beta 6.29 4.68E−05 Xq28-CGA high GNGT1|2792 guanine nucleotide binding protein (G protein), g

22.02 2.12E−19 Xq28-CGA high GPR126|57211 3.45 5.41E−07 Xq28-CGA high GPR152|390212 G protein-coupled receptor 152 3.67 3.07E−05 Xq28-CGA high GPR158|57512 G protein-coupled receptor 158 7.06 2.44E−09 Xq28-CGA high GPR81|27198 hydroxycarboxylic acid receptor 1 4.5 9.46E−07 Xq28-CGA high GRB14|2888 growth factor receptor-bound protein 14 3.68 6.32E−05 Xq28-CGA high GRIA2|2891 glutamate receptor, ionotropic, AMPA 2 6.35 3.90E−10 Xq28-CGA high GSTT2|2953 glutathione S-transferase theta 2 3.36 3.47E−05 Xq28-CGA high GTSF1|121355 gametocyte specific factor 1 10.19 5.52E−13 Xq28-CGA high GUCY1B2|2974 guanylate cyclase 1, soluble, beta 2 (pseudogene

2.42 3.92E−06 Xq28-CGA high GULP1|51454 GULP, engulfment adaptor PTB domain containi

2.01 3.62E−05 Xq28-CGA high GYPE|2996 glycophorin E (MNS blood group) 2.37 2.66E−05 Xq28-CGA high HAPLN1|1404 hyaluronan and proteoglycan link protein 1 2.44 9.80E−06 Xq28-CGA high HAPLN2|60484 hyaluronan and proteoglycan link protein 2 2.02 1.21E−04 Xq28-CGA high HBE1|3046 hemoglobin, epsilon 1 17.69 6.64E−11 Xq28-CGA high HBG2|3048 hemoglobin, gamma G 3.68 1.18E−06 Xq28-CGA high HERC2P4|440362 hect domain and RLD 2 pseudogene 4 2.31 1.22E−09 Xq28-CGA high HFE2|148738 hemochromatosis type 2 (juvenile) 2.72 5.88E−05 Xq28-CGA high HFM1|164045 HFM1, ATP-dependent DNA helicase homolog (S

2.53 3.95E−07 Xq28-CGA high HHATL|57467 hedgehog acyltransferase-like 5.41 8.80E−06 Xq28-CGA high HHLA2|11148 HERV-H LTR-associating 2 3.23 3.53E−06 Xq28-CGA high HIST1H2BF|8343 histone cluster 1, H2bf 2.45 3.66E−06 Xq28-CGA high HIST2H4A|8370 histone cluster 2, H4a 2.03 1.36E−05 Xq28-CGA high HIVEP3|59269 human immunodeficiency virus type I enhancer 2.08 3.98E−08 Xq28-CGA high HMGA2|8091 high mobility group AT-hook 2 5.05 1.37E−08 Xq28-CGA high HOOK1|51361 hook microtubule-tethering protein 1 2.89 5.09E−06 Xq28-CGA high HORMAD1|84072 HORMA domain containing 1 26.19 2.43E−06 Xq28-CGA high HOXA1|3198 homeobox A1 2.06 4.88E−05 Xq28-CGA high HOXA2|3199 homeobox A2 2.1 0.000153759 Xq28-CGA high HOXA3|3200 homeobox A3 2.87 7.97E−05 Xq28-CGA high HOXC10|3226 homeobox C10 2.47 2.92E−06 Xq28-CGA high HOXD10|3236 homeobox D10 2.1 4.39E−06 Xq28-CGA high HOXD11|3237 homeobox D11 2.87 1.30E−05 Xq28-CGA high HOXD13|3239 homeobox D13 6.95 1.38E−11 Xq28-CGA high HS3ST5|222537 heparan sulfate (glucosamine) 3-O-sulfotransfer

3.04 8.25E−06 Xq28-CGA high HSD17B3|3293 hydroxysteroid (17-beta) dehydrogenase 3 2.34 1.58E−05 Xq28-CGA high HSPC072|29075 long intergenic non-protein coding RNA 652 3.03 6.30E−09 Xq28-CGA high HTN1|3346 histatin 1 27.42 4.20E−05 Xq28-CGA high HTR2C|3358 5-hydroxytryptamme (serotonin) receptor 2C, G 3.58 9.07E−14 Xq28-CGA high HTR3E|285242 5-hydroxytryptamine (serotonin) receptor 3E, io

2.43 3.95E−08 Xq28-CGA high HULC|728655 hepatocellular carcinoma up-regulated long non

28.25 1.12E−08 Xq28-CGA high HYDIN|54768 HYDIN, axonemal central pair apparatus protein 2.82 3.89E−05 Xq28-CGA high ID4|3400 inhibitor of DNA binding 4, dominant negative h

2.5 7.97E−05 Xq28-CGA high IGF2BP3|10643 insulin-like growth factor 2 mRNA binding protei

2.58 4.48E−06 Xq28-CGA high IGFN1|91156 immunoglobulin-like and fibronectin type III don

2.41 1.67E−06 Xq28-CGA high IL13RA2|3598 interleukin 13 receptor, alpha 2 41.62 3.72E−14 Xq28-CGA high IL1RAPL1|11141 interleukin 1 receptor accessory protein-like 1 5.55 3.11E−05 Xq28-CGA high IL31RA|133396 interleukin 31 receptor A 2.54 0.000141763 Xq28-CGA high INADL|10207 InaD-like (Drosophila) 2.11 1.36E−04 Xq28-CGA high INTU|27152 inturned planar cell polarity protein 2.06 1.94E−08 Xq28-CGA high IQUB|154865 IQ motif and ubiquitin domain containing 2.22 1.03E−07 Xq28-CGA high ISL2|64843 ISL LIM homeobox 2 4.66 1.46E−08 Xq28-CGA high ITGB3|3690 integrin, beta 3 (platelet glycoprotein IIIa, antige

2.42 1.98E−05 Xq28-CGA high ITPRIPL1|150771 inositol 1,4,5-trisphosphate receptor interacting 2.42 1.44E−05 Xq28-CGA high KC6|641516 keratoconus gene 6 2.67 4.58E−11 Xq28-CGA high KCNA6|3742 potassium voltage-gated channel, shaker-relate

2.36 6.63E−05 Xq28-CGA high KCNAB3|9196 potassium voltage-gated channel, shaker-relate

2.09 1.68E−05 Xq28-CGA high KCNC2|3747 potassium voltage-gated channel, Shaw-related

2.09 2.21E−08 Xq28-CGA high KCNH5|27133 potassium voltage-gated channel, subfamily H (e

2.6 5.13E−12 Xq28-CGA high KCNJ10|3766 potassium inwardly-rectifying channel, subfamil

3.49 6.79E−08 Xq28-CGA high KCNMB2|10242 potassium large conductance calcium-activated

2.34 1.16E−08 Xq28-CGA high KCNS1|3787 potassium voltage-gated channel, delayed-rectif

2.67 4.00E−05 Xq28-CGA high KIAA0664P3|1001323 clustered mitochondria (cluA/CLU1) homolog ps

2.76 6.68E−05 Xq28-CGA high KIAA1324L|222223 KIAA1324-like 2.71 1.38E−07 Xq28-CGA high KIAA1377|57562 2.39 2.61E−07 Xq28-CGA high KIAA1383|54627 microtubule-associated protein 10 2.54 7.63E−08 Xq28-CGA high KIF17|57576 kinesin family member 17 2.73 1.27E−04 Xq28-CGA high KIF5A|3798 kinesin family member 5A 3.68 1.28E−09 Xq28-CGA high KLF14|136259 Kruppel-like factor 14 4.57 1.86E−11 Xq28-CGA high KLF17|128209 Kruppel-like factor 17 2.17 2.09E−05 Xq28-CGA high KLHL13|90293 kelch-like family member 13 4.48 5.29E−05 Xq28-CGA high KLHL23|151230 kelch-fike family member 23 2.44 4.64E−07 Xq28-CGA high KLK2|3817 kallikrein-related peptidase 2 6.77 2.54E−08 Xq28-CGA high KRT18|3875 keratin 18 5.23 5.86E−08 Xq28-CGA high LCTL|197021 lactase-like 2.59 3.49E−05 Xq28-CGA high LGALS12|85329 lectin, galactoside-binding, soluble, 12 3.39 3.69E−08 Xq28-CGA high LIN28A|79727 lin-28 homolog A (C. elegans) 2.57 5.88E−07 Xq28-CGA high LIN28B|389421 lin-28 homolog B (C. elegans) 5.07 1.09E−08 Xq28-CGA high LMOD2|442721 leiomodin 2 (cardiac) 2.2 3.12E−07 Xq28-CGA high LOC100128675|100128675 15.63 6.73E−07 Xq28-CGA high LOC100130386|100130386 2.69 5.98E−06 Xq28-CGA high LOC100133469|100133469 1402.15 4.13E−30 Xq28-CGA high LOC100190938|100190938 3.14 3.54E−08 Xq28-CGA high LOC100240726|100240726 2.76 5.77E−05 Xq28-CGA high LOC100271722|100271722 2.04 1.35E−05 Xq28-CGA high LOC116437|116437 2.23 2.01E−05 Xq28-CGA high LOC134466|134466 5.45 2.54E−09 Xq28-CGA high LOC146481|146481 8.29 1.42E−04 Xq28-CGA high LOC148824|148824 2.32 2.45E−05 Xq28-CGA high LOC150197|150197 2.73 4.51E−06 Xq28-CGA high LOC153910|153910 5.04 1.12E−10 Xq28-CGA high LOC162632|162632 2.36 7.79E−05 Xq28-CGA high LOC220594|220594 3.17 6.92E−05 Xq28-CGA high LOC220930|220930 2.19 0.000106118 Xq28-CGA high LOC257358|257358 2.12 9.99E−07 Xq28-CGA high LOC285419|285419 2.17 9.57E−05 Xq28-CGA high LOC285501|285501 4.41 5.54E−17 Xq28-CGA high LOC285548|285548 2.74 9.57E−07 Xq28-CGA high LOC286002|286002 5.97 2.13E−07 Xq28-CGA high LOC286467|286467 3.3 3.82E−09 Xq28-CGA high LOC339535|339535 3.3 4.53E−06 Xq28-CGA high LOC374491|374491 2.68 6.92E−08 Xq28-CGA high LOC399815|399815 chromosome 10 open reading frame 88 pseudog

2.04 1.51E−05 Xq28-CGA high LOC399959|399959 4.61 8.73E−07 Xq28-CGA high LOC440563|440563 2.05 1.08E−05 Xq28-CGA high LOC440905|440905 2.84 5.41E−07 Xq28-CGA high LOC441046|441046 3.08 3.17E−08 Xq28-CGA high LOC441294|441294 4.98 1.05E−08 Xq28-CGA high LOC441601|441601 septin 7 pseudogene 3.35 3.65E−12 Xq28-CGA high LOC645323|645323 2.92 7.58E−07 Xq28-CGA high LOC646627|646627 8.95 6.72E−07 Xq28-CGA high LOC648691|648691 2.64 4.38E−09 Xq28-CGA high LOC728819|728819 6.45 1.05E−13 Xq28-CGA high LOC84740|84740 2.05 1.49E−07 Xq28-CGA high LPAR3|23566 lysophosphatidic acid receptor 3 3.19 8.77E−05 Xq28-CGA high LPPR1|54886 lipid phosphate phosphatase-related protein typ

4.08 2.89E−08 Xq28-CGA high LPPR5|163404 lipid phosphate phosphatase-related protein typ

2.13 5.11E−05 Xq28-CGA high LRCH2|57631 leucine-rich repeats and calponin homology (CH)

6.46 9.89E−09 Xq28-CGA high LRP4|4038 low density lipoprotein receptor-related protein 2.53 4.73E−08 Xq28-CGA high LRRC52|440699 leucine rich repeat containing 52 3.49 3.81E−05 Xq28-CGA high LRRC69|100130742 leucine rich repeat containing 69 3.12 9.90E−11 Xq28-CGA high LRRIQ1|84125 leucine-rich repeats and IQ motif containing 1 7.44 3.41E−07 Xq28-CGA high LYG2|254773 lysozyme G-like 2 4.85 3.08E−07 Xq28-CGA high MAEL|84944 maelstrom spermatogenic transposon silencer 3.41 2.44E−05 Xq28-CGA high MAGEA10|4109 melanoma antigen family A, 10 1422.65 7.86E−33 Xq28-CGA high MAGEA11|4110 melanoma antigen family A, 11 93.76 3.72E−22 Xq28-CGA high MAGEA12|4111 melanoma antigen family A, 12 1533.86 3.82E−40 Xq28-CGA high MAGEA1|4100 melanoma antigen family A, 1 (directs expressio

1309.3 3.67E−32 Xq28-CGA high MAGEA2|4101 melanoma antigen family A, 2 2276.53 1.98E−40 Xq28-CGA high MAGEA3|4102 melanoma antigen family A, 3 2434.59 3.72E−40 Xq28-CGA high MAGEA4|4103 melanoma antigen family A, 4 365.89 9.45E−18 Xq28-CGA high MAGEA5|4104 melanoma antigen family A, 5 10.12 3.15E−25 Xq28-CGA high MAGEA6|4105 melanoma antigen family A, 6 2536.59 3.81E−40 Xq28-CGA high MAGEA8|4107 melanoma antigen family A, 8 2.32 2.02E−05 Xq28-CGA high MAGEA9B|728269 melanoma antigen family A, 9B 11.92 2.73E−14 Xq28-CGA high MAGEB16|139604 melanoma antigen family B, 16 2.6 2.58E−19 Xq28-CGA high MAGEB1|4112 melanoma antigen family B, 1 4.62 1.91E−17 Xq28-CGA high MAGEB2|4113 melanoma antigen family B, 2 47.51 1.38E−19 Xq28-CGA high MAGEB6|158809 melanoma antigen family B, 6 8.62 4.45E−18 Xq28-CGA high MAGEC1|9947 melanoma antigen family C, 1 737.15 2.15E−30 Xq28-CGA high MAGEC2|51438 melanoma antigen family C, 2 2411.41 7.48E−26 Xq28-CGA high MAGEC3|139081 melanoma antigen family C, 3 3.64 2.47E−12 Xq28-CGA high MAOA|4128 monoamine oxidase A 2.94 1.23E−05 Xq28-CGA high MAP9|79884 microtubule-associated protein 9 4.12 2.29E−06 Xq28-CGA high MAT1A|4143 methionine adenosyltransferase I, alpha 5.07 2.73E−06 Xq28-CGA high MEGF10|84466 multiple EGF-like-domains 10 18.91 1.58E−09 Xq28-CGA high MGAT4C|25834 mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-a

7.44 2.17E−14 Xq28-CGA high MGC16121|84848 2.03 5.68E−05 Xq28-CGA high MMEL1|79258 membrane metallo-endopeptidase-like 1 3.01 4.77E−05 Xq28-CGA high MMP16|4325 matrix metallopeptidase 16 (membrane-inserte

4.58 1.21E−05 Xq28-CGA high MOG|4340 myelin oligodendrocyte glycoprotein 4.42 1.62E−05 Xq28-CGA high MORC1|27136 MORC famiy CW-type zinc finger 1 9.55 1.50E−10 Xq28-CGA high MPPED2|744 metallophosphoesterase domain containing 2 2.21 1.16E−04 Xq28-CGA high MRGPRX3|117195 MAS-related GPR, member X3 11.36 1.44E−10 Xq28-CGA high MS4A15|219995 membrane-spanning 4-domains, subfamily A, m

4.4 1.45E−04 Xq28-CGA high MST4|51765 3.18 5.54E−07 Xq28-CGA high MT1G|4495 metallothionein 1G 2.32 2.01E−05 Xq28-CGA high MT1H|4496 metallothionein 1H 2.55 4.65E−05 Xq28-CGA high MUC15|143662 mucin 15, cell surface associated 17.34 1.07E−11 Xq28-CGA high MYADML2|255275 myeloid-associated differentiation marker-like 2

2.07 5.51E−07 Xq28-CGA high MYBPC1|4604 myosin binding protein C, slow type 3.42 5.56E−07 Xq28-CGA high MYH13|8735 myosin, heavy chain 13, skeletal muscle 4.59 2.26E−08 Xq28-CGA high MYH15|22989 myosin, heavy chain 15 2.13 1.90E−06 Xq28-CGA high MYOT|9499 myotillin 2.45 6.28E−06 Xq28-CGA high MYOZ3|91977 myozenin 3 2.49 4.58E−05 Xq28-CGA high NAA11|84779 N(alpha)-acetyltransferase 11, NatA catalytic su

8.03 2.57E−18 Xq28-CGA high NBPF22P|285622 neuroblastoma breakpoint family, member 22, p

4.32 3.64E−08 Xq28-CGA high NBPF4|148545 neuroblastoma breakpoint family, member 4 10.14 8.18E−09 Xq28-CGA high NBPF6|653149 neuroblastoma breakpoint family, member 6 13.18 2.09E−07 Xq28-CGA high NCRNA00189|193629 long intergenic non-protein coding RNA 189 16.16 5.66E−07 Xq28-CGA high NEB|4703 nebulin 2.34 3.07E−09 Xq28-CGA high NECAB1|64168 N-terminal EF-hand calcium binding protein 1 2.02 1.13E−09 Xq28-CGA high NFE2L3|9603 nuclear factor, erythroid 2-like 3 2.68 2.30E−09 Xq28-CGA high NFIA|4774 nuclear factor I/A 2.24 9.57E−09 Xq28-CGA high NLGN3|54413 neuroligin 3 2.67 4.69E−06 Xq28-CGA high NLRP11|204801 NLR family, pyrin domain containing 11 5.18 5.32E−12 Xq28-CGA high NLRP4|147945 NLR family, pyrin domain containing 4 4.25 3.07E−09 Xq28-CGA high NOX4|50507 NADPH oxidase 4 3.66 2.75E−07 Xq28-CGA high NPY6R|4888 neuropeptide Y receptor Y6 (pseudogene) 3.12 4.69E−09 Xq28-CGA high NXPH1|30010 neurexophilin 1 3 3.58E−06 Xq28-CGA high OCIAD2|132299 OCIA domain containing 2 2.48 9.31E−05 Xq28-CGA high OCLM|10896 oculomedin 2.03 1.08E−09 Xq28-CGA high ODZ1|10178 teneurin transmembrane protein 1 2.23 1.64E−06 Xq28-CGA high OLFM3|118427 olfactomedin 3 2.32 9.03E−07 Xq28-CGA high OLIG2|10215 oligodendrocyte lineage transcription factor 2 25.54 3.80E−06 Xq28-CGA high OMP|4975 olfactory marker protein 2.38 1.18E−08 Xq28-CGA high OR1J2|26740 olfactory receptor, family 1, subfamily J, membe

2.01 6.40E−06 Xq28-CGA high OR2A1|346528 olfactory receptor, family 2, subfamily A, membe

3.14 2.58E−06 Xq28-CGA high OR2A25|392138 olfactory receptor, family 2, subfamily A, membe

5.45 9.70E−07 Xq28-CGA high OR2A4|79541 olfactory receptor, family 2, subfamily A, membe

3.39 4.54E−06 Xq28-CGA high OR2A7|401427 olfactory receptor, family 2, subfamily A, membe

2.49 2.32E−05 Xq28-CGA high OR2A9P|441295 olfactory receptor, family 2, subfamily A, membe

3.33 1.98E−07 Xq28-CGA high OR2B6|26212 olfactory receptor, family 2, subfamily B, membe

2.16 1.03E−04 Xq28-CGA high OR2H2|7932 olfactory receptor, family 2, subfamily H, membe

6.93 5.96E−06 Xq28-CGA high OR51B5|282763 olfactory receptor, family 51, subfamily B, memb

4.35 3.04E−11 Xq28-CGA high OR56B4|196335 olfactory receptor, family 56, subfamily B, memb

4.94 7.66E−06 Xq28-CGA high OR7E5P|219445 olfactory receptor, family 7, subfamily E, membe

2.38 2.35E−12 Xq28-CGA high OR8A1|390275 olfactory receptor, family 8, subfamily A, membe

4.39 1.09E−20 Xq28-CGA high OXGR1|27199 oxoglutarate (alpha-ketoglutarate) receptor 1 3.49 0.000140551 Xq28-CGA high PAGE1|8712 P antigen family, member 1 (prostate associated

6.35 8.46E−11 Xq28-CGA high PAGE2B|389860 P antigen family, member 2B 19.39 1.50E−12 Xq28-CGA high PAGE5|90737 P antigen family, member 5 (prostate associated

2367.74 5.52E−23 Xq28-CGA high PAH|5053 phenylalanine hydroxylase 3.81 3.54E−06 Xq28-CGA high PALM3|342979 paralemmin 3 2.67 2.20E−05 Xq28-CGA high PANX3|116337 pannexin 3 3.87 4.49E−19 Xq28-CGA high PAR5|8123 Prader Willi/Angelman region RNA 5 2.13 1.30E−05 Xq28-CGA high PASD1|139135 PAS domain containing 1 2.29 5.56E−15 Xq28-CGA high PCDH7|5099 protocadherin 7 2.25 3.74E−05 Xq28-CGA high PCDHB18|54660 2.09 1.13E−04 Xq28-CGA high PCDHGA2|56113 protocadherin gamma subfamily A, 2 2.48 1.02E−05 Xq28-CGA high PCSK1|5122 proprotein convertase subtilisin/kexin type 1 3.29 3.12E−05 Xq28-CGA high PDC|5132 phosducin 3.81 1.02E−06 Xq28-CGA high PDIA2|64714 protein disulfide isomerase family A, member 2 3.74 3.41E−07 Xq28-CGA high PDK4|5166 pyruvate dehydrogenase kinase, isozyme 4 2.6 2.60E−05 Xq28-CGA high PEG10|23089 paternally expressed 10 2.16 9.13E−06 Xq28-CGA high PEX5L|51555 peroxisomal biogenesis factor 5-like 2.32 5.38E−07 Xq28-CGA high PGAM2|5224 phosphoglycerate mutase 2 (muscle) 2.01 1.81E−08 Xq28-CGA high PI15|51050 peptidase inhibitor 15 5.2 1.20E−06 Xq28-CGA high PKIA|5569 protein kinase (cAMP-dependent, catalytic) inhi

3.07 0.00012646 Xq28-CGA high PLAC1|10761 placenta-specific 1 3.58 1.67E−09 Xq28-CGA high PLCB1|23236 phospholipase C, beta 1 (phosphoinositide-speci

8.55 1.87E−19 Xq28-CGA high PLCB4|5332 phospholipase C, beta 4 12.5 4.71E−07 Xq28-CGA high PLCE1|51196 phospholipase C, epsilon 1 2.3 6.81E−05 Xq28-CGA high PLEKHB1|58473 pleckstrin homology domain containing, family B

3.79 3.13E−07 Xq28-CGA high PLS1|5357 plastin 1 2.64 6.71E−06 Xq28-CGA high PMFBP1|83449 polyamine modulated factor 1 binding protein 1 2.59 6.38E−08 Xq28-CGA high POU5F1B|5462 POU class 5 homeobox 1B 3.69 1.48E−09 Xq28-CGA high POU6F2|11281 POU class 6 homeobox 2 2.55 1.28E−12 Xq28-CGA high PPIEL|728448 peptidylprolyl isomerase E-like pseudogene 2.09 3.83E−05 Xq28-CGA high PPP1R1B|84152 protein phosphatase 1, regulatory (inhibitor) sub

2.91 5.01E−05 Xq28-CGA high PPP1R1C|151242 protein phosphatase 1, regulatory (inhibitor) sub

5.08 1.17E−10 Xq28-CGA high PPP1R9A|55607 protein phosphatase 1, regulatory subunit 9A 2.39 9.20E−07 Xq28-CGA high PPP2R2B|5521 protein phosphatase 2, regulatory subunit B, bet

2.35 9.31E−05 Xq28-CGA high PRKAA2|5563 protein kinase, AMP-activated, alpha 2 catalytic

3.72 1.16E−05 Xq28-CGA high PRSS21|10942 protease, serine, 21 (testisin) 4.9 5.77E−05 Xq28-CGA high PSG9|5678 pregnancy specific beta-1-glycoprotein 9 2.87 3.35E−05 Xq28-CGA high PTN|5764 pleiotrophin 2.17 2.20E−05 Xq28-CGA high PTPN20B|26095 5.03 1.97E−05 Xq28-CGA high PYY2|23615 peptide YY, 2 (pseudogene) 2.06 1.36E−04 Xq28-CGA high RAB26|25837 RAB26, member RAS oncogene family 2.73 3.05E−09 Xq28-CGA high RAB3IP|117177 RAB3A interacting protein 2.68 5.23E−07 Xq28-CGA high RAPGEF4|11069 Rap guanine nucleotide exchange factor (GEF) 4 2.89 2.90E−05 Xq28-CGA high RARB|5915 retinoic acid receptor, beta 4.72 1.52E−06 Xq28-CGA high RBM20|282996 RNA binding motif protein 20 6.07 4.51E−07 Xq28-CGA high RBMS3|27303 RNA binding motif, single stranded interacting p

2.59 2.84E−05 Xq28-CGA high RCOR2|283248 REST corepressor 2 2.96 5.46E−05 Xq28-CGA high RFPL4B|442247 ret finger protein-like 4B 2.53 5.32E−06 Xq28-CGA high RFX4|5992 regulatory factor X, 4 (influences HLA class II exp

2.57 4.43E−10 Xq28-CGA high RGNEF|64283 Rho guanine nucleotide exchange factor (GEF) 2

2.23 3.17E−06 Xq28-CGA high RLBP1|6017 retinaldehyde binding protein 1 7.09 8.78E−09 Xq28-CGA high RNASE10|338879 ribonuclease, RNase A family, 10 (non-active) 2.01 0.000118574 Xq28-CGA high RND2|8153 Rho family GTPase 2 3.68 1.26E−08 Xq28-CGA high RNF175|285533 ring finger protein 175 10.89 8.92E−10 Xq28-CGA high RPS15AP10|728963 ribosomal protein S15a pseudogene 10 2.07 1.12E−07 Xq28-CGA high RYR2|6262 ryanodine receptor 2 (cardiac) 3.28 2.76E−06 Xq28-CGA high SCAND3|114821 2.01 5.38E−05 Xq28-CGA high SCARNA16|677781 small Cajal body-spedfic RNA 16 2.43 7.17E−07 Xq28-CGA high SCN2A|6326 sodium channel, voltage-gated, type II, alpha sub

2.19 1.44E−06 Xq28-CGA high SCN9A|6335 sodium channel, voltage-gated, type IX, alpha su

4.32 2.23E−06 Xq28-CGA high SCRG1|11341 stimulator of chondrogenesis 1 5.17 1.12E−04 Xq28-CGA high SCRN1|9805 secemin 1 4.15 6.09E−07 Xq28-CGA high SEMA3E|9723 sema domain, immunoglobulin domain (Ig), sho

9.39 5.40E−09 Xq28-CGA high SERPINA5|5104 serpin peptidase inhibitor, clade A (alpha-1 antip

6.08 1.42E−07 Xq28-CGA high SH2D6|284948 SH2 domain containing 6 2.21 3.12E−06 Xq28-CGA high SHROOM3|57619 shroom family member 3 4.64 1.46E−08 Xq28-CGA high SKAP1|8631 src kinase associated phosphoprotein 1 3.16 7.20E−05 Xq28-CGA high SLC10A4|201780 solute carrier family 10, member 4 2.53 1.80E−09 Xq28-CGA high SLC15A2|6565 solute carrier family 15 (oligopeptide transporte

2.31 1.64E−08 Xq28-CGA high SLC18A1|6570 solute carrier family 18 (vesicular monoamine tr

2.12 7.98E−05 Xq28-CGA high SLC22A13|9390 solute carrier family 22 (organic anion/urate trar

2.42 7.74E−05 Xq28-CGA high SLC23A3|151295 solute carrier family 23, member 3 2.14 9.02E−07 Xq28-CGA high SLC26A4|5172 solute carrier family 26 (anion exchanger), mem

3.23 4.85E−07 Xq28-CGA high SLC26A7|115111 solute carrier family 26 (anion exchanger), mem

2.43 3.31E−05 Xq28-CGA high SLC30A8|160026 solute carrier family 30 (zinc transporter), memb

5.18 1.88E−13 Xq28-CGA high SLC44A5|204962 solute carrier family 44, member 5 4.46 1.06E−08 Xq28-CGA high SLC5A12|159963 solute carrier family 5 (sodium/monocarboxylat

4.14 3.14E−12 Xq28-CGA high SLC6A13|6540 solute carrier family 6 (neurotransmitter transpo

2.08 2.53E−05 Xq28-CGA high SLC9A11|284525 solute carrier family 9, member C2 (putative) 3.07 5.28E−08 Xq28-CGA high SLCO1A2|6579 solute carrier organic anion transporter family, n

18.61 2.14E−18 Xq28-CGA high SMC1B|27127 structural maintenance of chromosomes 1B 2.52 3.15E−06 Xq28-CGA high SMEK3P|139420 SMEK homolog 3, suppressor of mek1 (Dictyoste

3.05 3.36E−17 Xq28-CGA high SMYD1|150572 SET and MYND domain containing 1 3.11 7.47E−08 Xq28-CGA high SOHLH1|402381 spermatogenesis and oogenesis specific basic he

3.48 8.79E−07 Xq28-CGA high SORL1|6653 sortilin-related receptor, L(DLR class) A repeats

2.27 2.39E−05 Xq28-CGA high SOSTDC1|25928 sclerostin domain containing 1 5.8 4.30E−05 Xq28-CGA high SP140L|93349 SP140 nuclear body protein-like 2.23 1.21E−10 Xq28-CGA high SPAG17|200162 sperm associated antigen 17 2.04 4.74E−06 Xq28-CGA high SPAG4|6676 sperm associated antigen 4 2.37 2.61E−07 Xq28-CGA high SPATA17|128153 spermatogenesis associated 17 2.17 4.63E−06 Xq28-CGA high SPERT|220082 spermatid associated 3.05 6.01E−06 Xq28-CGA high SPP1|6696 secreted phosphoprotein 1 3.57 1.36E−07 Xq28-CGA high SPRY4|81848 sprouty homolog 4 (Drosophila) 2.46 4.90E−07 Xq28-CGA high SSX1|6756 synovial sarcoma, X breakpoint 1 11.7 1.86E−06 Xq28-CGA high SSX2|6757 synovial sarcoma, X breakpoint 2 28.85 6.07E−22 Xq28-CGA high SSX5|6758 synovial sarcoma, X breakpoint 5 7.49 3.80E−06 Xq28-CGA high SSX6|280657 synovial sarcoma, X breakpoint 6 (pseudogene) 5.71 1.61E−06 Xq28-CGA high ST6GALNAC5|81849 ST6 (alpha-N-acetyl-neuraminyl-2,3-beta-galact

4.3 9.70E−07 Xq28-CGA high STARD4|134429 StAR-related lipid transfer (START) domain conta

2.15 4.31E−05 Xq28-CGA high STK31|56164 serine/threonine kinase 31 7.76 2.18E−11 Xq28-CGA high STK33|65975 serine/threonine kinase 33 2.69 4.34E−05 Xq28-CGA high SUMO4|387082 small ubiquitin-like modifier 4 2.18 2.64E−07 Xq28-CGA high SV2A|9900 synaptic vesicle glycoprotein 2A 6.7 2.15E−12 Xq28-CGA high SYT1|6857 synaptotagmin I 3.35 1.97E−08 Xq28-CGA high SYTL5|94122 synaptotagmin-like 5 5.5 9.53E−07 Xq28-CGA high TAGLN3|29114 transgelin 3 3.39 2.57E−06 Xq28-CGA high TAS2R19|259294 taste receptor, type 2, member 19 2.03 5.58E−05 Xq28-CGA high TCL6|27004 T-cell leukemia/lymphoma 6 (non-protein coding

18.82 2.79E−16 Xq28-CGA high TEKT2|27285 tektin 2 (testicular) 2.94 3.62E−08 Xq28-CGA high TFDP3|51270 transcription factor Dp family, member 3 3.27 2.47E−06 Xq28-CGA high TF|7018 transferrin 3.99 1.41E−04 Xq28-CGA high TIGD4|201798 tigger transposable element derived 4 2.31 1.27E−08 Xq28-CGA high TKTL2|84076 transketolase-like 2 2.13 4.05E−11 Xq28-CGA high TMEM195|392636 alkylglycerol monooxygenase 5.68 1.19E−05 Xq28-CGA high TMEM22|80723 solute carrier family 35, member G2 2.26 8.89E−05 Xq28-CGA high TMEM25|84866 transmembrane protein 25 2.95 2.50E−05 Xq28-CGA high TMEM84|283673 4.13 3.13E−07 Xq28-CGA high TMPRSS5|80975 transmembrane protease, serine 5 2.07 4.57E−07 Xq28-CGA high TP53TG3B|729355 TP53 target 3B 2.47 6.05E−06 Xq28-CGA high TPD52L1|7164 tumor protein D52-like 1 3.17 1.31E−07 Xq28-CGA high TPTE2P1|646405 transmembrane phosphoinositide 3-phosphatas

2.68 1.82E−05 Xq28-CGA high TPTE|7179 transmembrane phosphatase with tensin homo

62.08 1.22E−24 Xq28-CGA high TRIM17|51127 tripartite motif containing 17 2.99 8.69E−09 Xq28-CGA high TRIM36|55521 tripartite motif containing 36 2.06 9.96E−06 Xq28-CGA high TRIM54|57159 tripartite motif containing 54 2.95 3.90E−06 Xq28-CGA high TRIM6|117854 tripartite motif containing 6 2.29 4.44E−06 Xq28-CGA high TRIM9|114088 tripartite motif containing 9 2.23 2.74E−06 Xq28-CGA high TRPM3|80036 transient receptor potential cation channel, sub

3.46 6.67E−06 Xq28-CGA high TSNAX-DISC1|100303

TSNAX-DISC1 readthrough (NMD candidate) 4.38 1.43E−04 Xq28-CGA high TSPAN5|10098 tetraspanin 5 2.06 2.45E−05 Xq28-CGA high TTLL7|79739 tubulin tyrosine ligase-like family, member 7 2.28 0.00013952 Xq28-CGA high TUBA3C|7278 tubulin, alpha 3c 12.67 4.33E−16 Xq28-CGA high UGT2A1|10941 UDP glucuronosyltransferase 2 family, polypepti

2.06 4.25E−09 Xq28-CGA high UGT8|7368 UDP glycosyltransferase 8 5.41 2.21E−09 Xq28-CGA high UNC80|285175 unc-80 homolog (C. elegans) 2.57 1.40E−06 Xq28-CGA high VCX3A|51481 variable charge, X-linked 3A 19.16 1.39E−20 Xq28-CGA high VCX3B|425054 variable charge, X-linked 3B 5.79 1.15E−13 Xq28-CGA high VCX|26609 variable charge, X-linked 13.04 4.05E−14 Xq28-CGA high VWDE|221806 von Willebrand factor D and EGF domains 2.35 4.27E−06 Xq28-CGA high WDR52|55779 2.03 1.31E−06 Xq28-CGA high WISP3|8838 WNT1 inducible signaling pathway protein 3 2.47 2.26E−06 Xq28-CGA high WNK4|65266 WNK lysine deficient protein kinase 4 3.12 2.06E−05 Xq28-CGA high XAGE1D|9503 X antigen family, member 1D 19239.33 1.24E−29 Xq28-CGA high XIRP2|129446 xin actin-binding repeat containing 2 2.56 1.64E−06 Xq28-CGA high XIST|7503 X inactive specific transcript (non-protein coding

21.76 9.36E−06 Xq28-CGA high XK|7504 X-linked Kx blood group (McLeod syndrome) 2.62 3.75E−05 Xq28-CGA high ZBTB8B|728116 zinc finger and BTB domain containing 8B 3.07 3.47E−06 Xq28-CGA high ZIC1|7545 Zic family member 1 2.51 6.91E−05 Xq28-CGA high ZNF157|7712 zinc finger protein 157 2.84 4.19E−09 Xq28-CGA high ZNF214|7761 zinc finger protein 214 2.73 1.45E−04 Xq28-CGA high ZNF229|7772 zinc finger protein 229 3.24 1.34E−07 Xq28-CGA high ZNF280A|129025 zinc finger protein 280A 4.77 1.54E−11 Xq28-CGA high ZNF300|91975 zinc finger protein 300 3.32 3.73E−10 Xq28-CGA high ZNF334|55713 zinc finger protein 334 5.34 1.99E−07 Xq28-CGA high ZNF541|84215 zinc finger protein 541 2.08 3.32E−06 Xq28-CGA high ZNF556|80032 zinc finger protein 556 5.97 6.11E−08 Xq28-CGA high ZNF560|147741 zinc finger protein 560 29.67 1.43E−13 Xq28-CGA high ZNF595|152687 zinc finger protein 595 9.28 4.47E−18 Xq28-CGA high ZNF648|127665 zinc finger protein 648 4.46 1.27E−07 Xq28-CGA high ZNF660|285349 zinc finger protein 660 3.17 7.07E−06 Xq28-CGA high ZNF695|57116 zinc finger protein 695 2.98 1.12E−05 Xq28-CGA high ZNF883|169834 zinc finger protein 883 5.3 1.04E−10 Xq28-CGA high ZSCAN12P1|221584 zinc finger and SCAN domain containing 12 pseu

3.43 2.36E−07 Xq28-CGA high ZSCAN23|222696 zinc finger and SCAN domain containing 23 3.3 3.28E−05 Xq28-CGA high ADAMTS2|9509 ADAM metallopeptidase with thrombospondin t

2.25 3.02E−05 Xq28-CGA low ADARB2|105 adenosine deaminase, RNA-specific, B2 (non-fun

3.51 1.54E−05 Xq28-CGA low ADCY2|108 adenylate cyclase 2 (brain) 12.12 1.54E−05 Xq28-CGA low ADRA2C|152 adrenoceptor alpha 2C 4 6.20E−05 Xq28-CGA low AP3B2|8120 adaptor-related protein complex 3, beta 2 subun

2.33 1.80E−05 Xq28-CGA low ARHGAP8|23779 Rho GTPase activating protein 8 3.71 8.66E−08 Xq28-CGA low ARHGEF4|50649 Rho guanine nucleotide exchange factor (GEF) 4 3.29 2.17E−06 Xq28-CGA low ARSI|340075 arylsulfatase family, member I 2.33 9.24E−05 Xq28-CGA low ATP1A3|478 ATPase, Na+/K+ transporting, alpha 3 polypeptid

2.75 1.32E−04 Xq28-CGA low B3GAT1|27087 beta-1,3-glucuronyltransferase 1 (glucuronosyltr

4.79 2.81E−04 Xq28-CGA low BIK|638 BCL2-interacting killer (apoptosis-inducing) 2.48 3.49E−05 Xq28-CGA low BRSK2|9024 BR serine/threonine kinase 2 6.57 2.24E−08 Xq28-CGA low C10orf116|10974 2.03 1.21E−04 Xq28-CGA low C10orf93|255352 8.71 1.13E−07 Xq28-CGA low C15orf59|388135 2.63 2.96E−07 Xq28-CGA low C21orf121|150142 2.23 1.38E−05 Xq28-CGA low C5orf38|153571 16.07 9.72E−11 Xq28-CGA low CACNA1B|774 calcium channel, voltage-dependent, N type, alp

2.79 7.72E−05 Xq28-CGA low CACNA1H|8912 calcium channel, voltage-dependent, T type, alp

2.99 1.56E−09 Xq28-CGA low CAPG|822 capping protein (actin filament), gelsolin-like 2.73 8.59E−06 Xq28-CGA low CBFA2T3|863 core-binding factor, runt domain, alpha subunit

2.07 7.68E−05 Xq28-CGA low CCDC64|92558 coiled-coil domain containing 64 2.34 5.12E−05 Xq28-CGA low CDHR1|92211 cadherin-related family member 1 2.47 3.35E−06 Xq28-CGA low CEBPA|1050 CCAAT/enhancer binding protein (C/EBP), alpha 2.01 2.45E−06 Xq28-CGA low CHRFAM7A|89832 CHRNA7 (cholinergic receptor, nicotinic, alpha 7

2.79 3.51E−04 Xq28-CGA low CHRNA7|1139 cholinergic receptor, nicotinic, alpha 7 (neurona

3.79 1.01E−07 Xq28-CGA low CIDEA|1149 cell death-inducing DFFA-like effector a 5.47 0.000131166 Xq28-CGA low CPNE7|27132 copine VII 3.07 7.29E−07 Xq28-CGA low CYS1|192668 cystin 1 2.53 1.72E−06 Xq28-CGA low DARC|2532 2.1 4.54E−05 Xq28-CGA low DGCR5|26220 DiGeorge syndrome critical region gene 5 (non-p

4.08 3.25E−10 Xq28-CGA low DKFZp779M0652|374387 2.25 1.43E−08 Xq28-CGA low DMRT2|10655 doublesex and mab-3 related transcription facto

3.59 5.31E−05 Xq28-CGA low DOC2B|8447 double C2-like domains, beta 2.14 2.60E−04 Xq28-CGA low DPYSL4|10570 dihydropyrimidinase-like 4 2.48 9.03E−05 Xq28-CGA low DUSP8|1850 dual specificity phosphatase 8 2.02 0.000253945 Xq28-CGA low DYNLRB2|83657 dynein, light chain, roadblock-type 2 2.15 6.20E−05 Xq28-CGA low EMID2|136227 collagen, type XXVI, alpha 1 2.74 2.90E−07 Xq28-CGA low FAM171A1|221061 family with sequence similarity 171, member A1 2.19 0.000114552 Xq28-CGA low FAM19A5|25817 family with sequence similarity 19 (chemokine (

5.61 5.22E−06 Xq28-CGA low FIBCD1|84929 fibrinogen C domain containing 1 3.2 4.22E−05 Xq28-CGA low FOXF2|2295 forkhead box F2 2.38 4.92E−05 Xq28-CGA low FOXQ1|94234 forkhead box Q1 2.15 9.40E−05 Xq28-CGA low FZD8|8325 frizzled class receptor 8 2.12 2.84E−04 Xq28-CGA low GABBR2|9568 gamma-aminobutyric acid (GABA) B receptor, 2 2.41 4.17E−08 Xq28-CGA low GABRA5|2558 gamma-aminobutyric acid (GABA) A receptor, al

4.93 2.66E−07 Xq28-CGA low GABRG3|2567 gamma-aminobutyric acid (GABA) A receptor, ga

12.79 9.85E−05 Xq28-CGA low GAS6|2621 growth arrest-specific 6 2.23 7.12E−07 Xq28-CGA low GCNT4|51301 glucosaminyl (N-acetyl) transferase 4, core 2 2.51 1.70E−05 Xq28-CGA low GMPR|2766 guanosine monophosphate reductase 3.05 1.49E−05 Xq28-CGA low GNAL|2774 guanine nucleotide binding protein (G protein),

4.64 1.17E−09 Xq28-CGA low GNAO1|2775 guanine nucleotide binding protein (G protein),

2.9 1.15E−04 Xq28-CGA low GOLGA7B|401647 golgin A7 family, member B 2.13 0.000106118 Xq28-CGA low GRID1|2894 glutamate receptor, ionotropic, delta 1 2.51 9.48E−10 Xq28-CGA low GSG1L|146395 GSG1-like 3.08 2.72E−06 Xq28-CGA low HAR1A|768096 highly accelerated region 1A (non-protein coding

3.32 5.76E−12 Xq28-CGA low HAR1B|768097 highly accelerated region 1B (non-protein coding

3.57 1.45E−10 Xq28-CGA low HCN2|610 hyperpolarization activated cyclic nucleotide-gat

2.25 1.88E−04 Xq28-CGA low HRH3|11255 histamine receptor H3 2.92 8.37E−07 Xq28-CGA low HS3ST2|9956 heparan sulfate (glucosamine) 3-O-sulfotransfer

3.09 1.23E−05 Xq28-CGA low HSPB8|26353 heat shock 22 kDa protein 8 3.83 1.67E−05 Xq28-CGA low HUNK|30811 hormonally up-regulated Neu-associated kinase 2.82 0.000262353 Xq28-CGA low IRX1|79192 iroquois homeobox 1 6.16 2.43E−06 Xq28-CGA low IRX2|153572 iroquois homeobox 2 9.36 1.54E−10 Xq28-CGA low ITGB1BP3|27231 nicotinamide riboside kinase 2 6.72 2.16E−06 Xq28-CGA low KCNH4|23415 potassium voltage-gated channel, subfamily H (e

2.45 1.31E−06 Xq28-CGA low KIAA1543|57662 calmodulin regulated spectrin-associated protei

3.57 1.60E−06 Xq28-CGA low KIF1A|547 kinesin family member 1A 3.31 2.82E−05 Xq28-CGA low KIF26A|26153 kinesin family member 26A 3.24 9.53E−15 Xq28-CGA low KNDC1|85442 kinase non-catalytic C-lobe domain (KIND) conta

7.08 5.98E−16 Xq28-CGA low L1CAM|3897 L1 cell adhesion molecule 3.61 1.67E−04 Xq28-CGA low LCE2A|353139 late cornified envelope 2A 5.9 2.62E−04 Xq28-CGA low LIMS2|55679 LIM and senescent cell antgen-like domains 2 2.04 8.94E−06 Xq28-CGA low LOC100127888|100127888 2.11 2.25E−04 Xq28-CGA low LOC284837|284837 2.08 2.81E−06 Xq28-CGA low LOC338651|338651 2.69 8.61E−07 Xq28-CGA low LOC389458|389458 2.08 2.38E−04 Xq28-CGA low LOC440925|440925 2.4 6.65E−05 Xq28-CGA low LOC80054|80054 2.14 2.35E−08 Xq28-CGA low LONRF3|79836 LON peptidase N-terminal domain and ring finge

2.61 2.90E−05 Xq28-CGA low LRRC26|389816 leucine rich repeat containing 26 4.44 4.41E−05 Xq28-CGA low LTF|4057 lactotransferrin 2.53 0.000291253 Xq28-CGA low MAGED4B|81557 melanoma antigen family D, 4B 4.16 5.73E−05 Xq28-CGA low MAGED4|728239 melanoma antigen family D, 4 4.37 6.71E−05 Xq28-CGA low MATK|4145 megakaryocyte-associated tyrosine kinase 2.86 9.34E−07 Xq28-CGA low MC1R|4157 melanocortin 1 receptor (alpha melanocyte stim

2.42 3.56E−05 Xq28-CGA low MEGF6|1953 multiple EGF-like-domains 6 4.12 9.53E−12 Xq28-CGA low MEIS3|56917 Meis homeobox 3 2.14 1.80E−04 Xq28-CGA low MNX1|3110 motor neuron and pancreas homeobox 1 7.94 5.05E−07 Xq28-CGA low NPDC1|56654 neural proliferation, differentiation and control,

2.07 7.67E−05 Xq28-CGA low NPTXR|23467 neuronal pentraxin receptor 3.04 1.35E−05 Xq28-CGA low NTN1|9423 netrin 1 3.61 1.47E−08 Xq28-CGA low NTNG2|84628 netrin G2 2.41 5.55E−08 Xq28-CGA low OCA2|4948 oculocutaneous albinism II 21.65 1.15E−05 Xq28-CGA low OLFM1|10439 olfactomedin 1 14.79 1.59E−15 Xq28-CGA low OTUD7A|161725 OTU deubiquitinase 7A 2.61 1.09E−07 Xq28-CGA low PANX2|56666 pannexin 2 3.37 4.51E−07 Xq28-CGA low PCBP3|54039 poly(rC) binding protein 3 3.31 1.77E−06 Xq28-CGA low PDE9A|5152 phosphodiesterase 9A 5.8 8.69E−09 Xq28-CGA low PGBD5|79605 piggyBac transposable element derived 5 2.11 1.56E−06 Xq28-CGA low PHF21B|112885 PHD finger protein 21B 3.98 3.59E−06 Xq28-CGA low PHYHD1|254295 phytanoyl-CoA dioxygenase domain containing

2.25 5.66E−05 Xq28-CGA low PLAC2|257000 tissue differentiation-indudng non-protein codin

6.62 1.05E−07 Xq28-CGA low PMEPA1|56937 prostate transmembrane protein, androgen indu

2.1 5.96E−05 Xq28-CGA low PNMA6A|84968 paraneoplastic Ma antigen family member 6A 3.11 4.76E−08 Xq28-CGA low PRODH|5625 proline dehydrogenase (oxidase) 1 3 5.90E−06 Xq28-CGA low PRR5-ARHGAP8|5531

PRR5-ARHGAP8 readthrough 9.56 2.42E−05 Xq28-CGA low PTK6|5753 protein tyrosine kinase 6 2.93 2.17E−06 Xq28-CGA low RADIL|55698 Ras association and DIL domains 4.59 1.96E−08 Xq28-CGA low RPS6KA2|6196 ribosomal protein S6 kinase, 90 kDa, polypeptide

2.38 1.22E−05 Xq28-CGA low SDK1|221935 sidekick cell adhesion molecule 1 2.27 8.66E−06 Xq28-CGA low SFTPD|6441 surfactant protein D 2.12 0.000262896 Xq28-CGA low SH3GL2|6456 SH3-domain GRB2-like 2 4.54 2.12E−04 Xq28-CGA low SIGLEC8|27181 sialic acid binding Ig-like lectin 8 2.58 0.000344343 Xq28-CGA low SLC16A6|9120 solute carrier family 16, member 6 4.38 2.79E−06 Xq28-CGA low SLC24A4|123041 solute carrier family 24 (sodium/potassium/calci

3.39 3.08E−05 Xq28-CGA low SLC39A12|221074 solute carrier family 39 (zinc transporter), memb

2.2 0.000277556 Xq28-CGA low SLPI|6590 secretory leukocyte peptidase inhibitor 3.31 0.000158902 Xq28-CGA low SNCB|6620 synuclein, beta 2.2 0.000254582 Xq28-CGA low SOX1|6656 SRY (sex determining region Y)-box 1 7.73 1.18E−08 Xq28-CGA low SP5|389058 Sp5 transcription factor 2.72 7.66E−05 Xq28-CGA low SYNC|81493 syncoilin, intermediate filament protein 2.17 1.99E−05 Xq28-CGA low TCERG1L|256536 transcription elongation regulator 1-like 2.67 1.42E−04 Xq28-CGA low TFF3|7033 trefoil factor 3 (intestinal) 4.18 1.26E−06 Xq28-CGA low TMPRSS13|84000 transmembrane protease, serine 13 6.69 6.70E−09 Xq28-CGA low TWIST2|117581 twist family bHLH transcription factor 2 3.28 7.49E−07 Xq28-CGA low USP43|124739 ubiquitin specific peptidase 43 6.39 4.55E−08 Xq28-CGA low VIPR1|7433 vasoactive intestinal peptide receptor 1 2.1 0.000161869 Xq28-CGA low WNT9B|7484 wingless-type MMTV integration site family, me

3.67 3.57E−06 Xq28-CGA low ZNF423|23090 zinc finger protein 423 2.29 3.19E−06 Xq28-CGA low

indicates data missing or illegible when filed

TABLE 4 Overlapping genes between no benefit/clinical benefit groups and TCGA Xq28-CGA-high/low subsets TCCGA Xq28-CGA high TCCGA Xq28-CGA low (n = 559) (n = 130) No benefit ABCA8, AKAP6, ANGPT1, ANKFN1, ANKRD20A3, ANKRD20A4, 0 (n = 975) ANKRD45, ANKRD7, ANO3, ATP1B2, B3GALNT1, C12orf56, C1QTNF3, C21orf90, C2orf66, C3orf30, C4orf19, CABP4, CADM4, CASP12, CCDC136, CFHR4, CFI, CNDP1, CSAG1, CSAG2, CSAG3, CYP26A1, DCAF4L2, DDX25, EFHC2, EGF, ELOVL2, EYA1, FAM106A, FAM81B, FGF2, FRAS1, GABRA3, GABRB1, GABRG2, GABRQ, GAGE12D, GALNT8, GAP43, GDNF, GNGT1, GPR158, GRIA2, GYPE, HHATL, HMGA2, HOXA2, HOXA3, HOXD10, HOXD11, HOXD13, IGFN1, IL13RA2, ISL2, KCNC2, KCNJ10, KCNMB2, KLF17, KLHL13, LCTL, LGALS12, LMOD2, LRP4, MAGEA1, MAGEA11, MAGEA12, MAGEA2, MAGEA3, MAGEA6, MAGEA8, MAGEA9B, MAGEB2, MAGEC1, MAGEC2, MAGEC3, MEGF10, MMEL1, MMP16, MRGPRX3, MYH13, NEB, NECAB1, NLRP4, NPY6R, NXPH1, OLFM3, OR56B4, PCDHB18, PCSK1, PEX5L, PI15, PLAC1, POU5F1B, PPP1R1C, PPP1R9A, PSG9, RAPGEF4, RBM20, RFPL4B, RND2, SCN2A, SERPINA5, SLC10A4, SLC18A1, SLC30A3, SLCO1A2, SOSTDC1, SPAG17, SPP1, SPRY4, SSX6, SV2A, SYT1, SYTL5, TEKT2, TPD52L1, TRIM9, TRPM3, TSPAN5, WNK4, XIRP2, XIST, ZNF334, ZNF541 Clinical benefit 0 ADCY2, ATP1A3, BIK, C5orf38, CPNE7, (n = 428) GOLGA7B, HS3ST2, IRX2, LRRC26, MNX1, SIGLEC8, SLC24A4, USP43

The following references were cited in this specification.

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OTHER EMBODIMENTS

While the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

The patent and scientific literature referred to herein establishes the knowledge that is available to those with skill in the art. All United States patents and published or unpublished United States patent applications cited herein are incorporated by reference. All published foreign patents and patent applications cited herein are hereby incorporated by reference. Genbank and NCBI submissions indicated by accession number cited herein are hereby incorporated by reference. All other published references, documents, manuscripts and scientific literature cited herein are hereby incorporated by reference.

While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention encompassed by the appended claims. 

1. A method of determining whether inhibition of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) in a subject with melanoma will result in clinical benefit in the subject comprising: obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether CTLA4 blockade will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample; or a method of determining whether inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject comprising: obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of a housekeeping gene in a reference sample; and determining whether CTLA4 blockade will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the housekeeping gene in the reference sample; or a method to predict a response of a subject with cancer to a CTLA4 therapy, the method comprising: (a) assaying for (i) aberrant expression of at least one resistant cancer-associated gene or miRNA in a biological sample from the subject, wherein the aberrant expression of the at least one resistant cancer-associated gene or miRNA is not present in the biological sample, or (ii) aberrant expression of at least one beneficial cancer-associated gene or miRNA in a biological sample from the subject, wherein the aberrant expression of the at least one beneficial cancer-associated gene or miRNA is present in the biological sample, and (b) predicting a response of the subject with cancer to a CTLA4 therapy to be positive based on the assaying.
 2. The method of claim 1, wherein the test sample is obtained from the melanoma tissue or from the tumor microenvironment or from tumor-infiltrating immune cells.
 3. The method of claim 1, wherein clinical benefit in the subject comprises complete or partial response as defined by response evaluation criteria in solid tumors (RECIST), stable disease as defined by RECIST, or long-term survival in spite of disease progression or response as defined by irRC criteria.
 4. The method of claim 1, wherein the test sample is obtained from the melanoma, and wherein the melanoma-associated gene comprises a gene on chromosome Xq28.
 5. The method of claim 1, wherein the test sample is obtained from the melanoma, wherein the melanoma-associated gene comprises a cancer germline antigen (CGA) gene; and determining that inhibition of CTLA4 in a subject with melanoma will not result in clinical benefit in the subject if the expression level of the CGA gene in the test sample is higher than the level of the CGA gene in the reference sample.
 6. The method of claim 5, wherein the CGA gene comprises melanoma-associated antigen 2 (MAGEA2), MAGEA3, MAGEA6, MAGEA12, chondrosarcoma associated gene 1 (CSAG1), CSAG2, CSAG3 or CSAG4.
 7. The method of claim 6, wherein the CGA gene is hypomethylated. 8.-9. (canceled)
 10. The method of claim 1, wherein the test sample is obtained from the melanoma, wherein the melanoma-associated gene comprises a pregnancy-specific glycoprotein (PSG) gene, a γ-aminobutyric acid (GABA) A receptor gene, an epithelial-to-mesenchymal transition gene, an embryonic development/differentiation gene, an angiogenesis gene, or an extracellular matrix (ECM) gene; and determining that inhibition of CTLA4 in a subject with melanoma will not result in clinical benefit in the subject if the expression level of the PSG gene, GABA A receptor gene, epithelial-to-mesenchymal transition gene, embryonic development/differentiation gene, angiogenesis gene, or extracellular matrix gene in the test sample is higher than the level of the corresponding gene in the reference sample. 11.-12. (canceled)
 13. The method of claim 10, wherein the GABA A receptor gene comprises gamma-aminobutyric acid type A receptor alpha 3 subunit (GABRA3), gamma-aminobutyric acid type A receptor beta 1 subunit (GABRB1), GABRB2, gamma-aminobutyric acid type A receptor gamma 2 subunit (GABRG2), gamma-aminobutyric acid type A receptor theta subunit (GABRQ), or gamma-aminobutyric acid type A receptor rho 1 subunit (GABRR1).
 14. The method of claim 10, wherein the epithelial-to-mesenchymal transition gene comprises claudin 1 (CLDN1), CLDN2, eyes absent homolog 1 (EYA1), snail family zinc finger 1 (SNAI1), transforming growth factor beta 2 (TGFB2), or wingless-type MMTV integration site family member 3 (WNT3). 15.-17. (canceled)
 18. The method of claim 1, wherein the test sample is obtained from the melanoma, wherein the melanoma-associated gene comprises MAGEA2, CSAG4, MAGEA2B, RP11-215P9, MAGEA12, CSAG1, GABRA3, CSAG3, makorin ring finger protein 9 (MKRN9P), keratin 8 pseudogene 8 (KRT8P8), MAGEA6, EYA1, CSAG2, RP11-379D21.3, MAGEC1, RP1-273G13.1, MAGEA3, miR-218-1, PSG11, X-inactive specific transcript (XIST), RP11-360D2.1, pregnancy specific beta-1-glycoprotein 10 pseudogene (PSG10P), miR-1262, tachykinin 3 (TAC3), PSG8, heat shock protein family B (small) member 3 (HSPB3), gap junction protein beta-6 (GJB6), PSG6, GABRQ, MAGEA1, MAGEA11 or MAGEA9B; and determining that inhibition of CTLA4 in a subject with melanoma will not result in clinical benefit in the subject if the expression level of the melanoma-associated gene in the test sample is higher than the level of the corresponding gene in the reference sample.
 19. The method of claim 1, wherein the test sample is obtained from the melanoma, and wherein the melanoma-associated gene comprises micro ribonucleic acid-211 (miR-211), miR-513A2, miR-185, or TRPM1; and determining that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of miR-211, miR-513A2, miR-185, or TRPM1 in the test sample is higher than the level of miR-211, miR-513A2, miR-185, or TRPM1, respectively, in the reference sample.
 20. The method of claim 1, wherein the test sample is obtained from the melanoma, and wherein the melanoma-associated gene comprises transient receptor potential cation channel subfamily M member 1 (TRPM1); and determining that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of TRPM1 in the test sample is higher than the level of TRPM1 in the reference sample.
 21. The method of claim 1, wherein the test sample is obtained from the melanoma or the infiltrating immune cells, and wherein the melanoma-associated gene comprises miR-211, MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, CSAG3, CSAG4; and determining that inhibition of CTLA4 in a subject with melanoma will not result in clinical benefit in the subject if the expression level of miR-211 in the test sample is lower than the level of miR-211 in the reference sample and if the expression level of MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, CSAG3, and CSAG4 in the test sample is higher than the level of the corresponding gene in the reference sample.
 22. The method of claim 1, wherein the test sample is obtained from the melanoma, and wherein the melanoma-associated gene comprises miR-211 and one or more of CD2, CD6, CXCL13, CD3D, CD3E, CD3G, LCK, T cell receptor alpha gene, T cell receptor beta gene, CD28, ICOS, EOMES, IL2RB, FASLG, SLAMF6, GNLY, GZMA, GZMB, GZMH, GZMK, PRF1, PTCRA, CD19, CD72, FCRL1/3, MS4A1, CTLA4, LAG3, FCRL1, FCRL3, CD5L, SIGLEC8, or FAIM3/TOSO; and determining that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of the melanoma-associated genes in the test sample is higher than the level of the gene in the reference sample.
 23. The method of claim 1, wherein the test sample is obtained from the melanoma and the melanoma-associated gene comprises CD2, CD6, CXCL13, CD3D, CD3E, CD3G, LCK, T cell receptor alpha gene, T cell receptor beta gene, CD28, ICOS, EOMES, IL2RB, FASLG, SLAMF6, GNLY, GZMA, GZMB, GZMH, GZMK, PRF1, PTCRA, CD19, CD72, FCRL1/3, MS4A1, CTLA4, LAG3, FCRL1, FCRL3, CD5L, SIGLEC8, or FAIM3/TOSO; and determining that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of the melanoma-associated gene in the test sample is higher than the level of the melanoma-associated gene in the reference sample.
 24. The method of claim 1, wherein the test sample is obtained from a melanoma tumor microenvironment, wherein the melanoma-associated gene comprises a T cell infiltration-associated gene, a receptor signaling gene, an activation gene, a cytotoxicity gene, a humoral immunity gene, or an immune inhibitory receptor gene; and determining that inhibition of CTLA4 in a subject with melanoma will result in clinical benefit in the subject if the expression level of the melanoma-associated gene in the test sample is higher than the level of the gene in the reference sample. 25.-52. (canceled)
 53. A composition for predicting no clinical benefit in response to CTLA4 therapy comprising a melanoma-associated gene, wherein the melanoma-associated gene comprises MAGEA2, MAGEA3, MAGEA6, MAGEA12, CSAG1, CSAG2, CSAG3, or CSAG4 synthesized complementary deoxyribonucleic acid (cDNA; or a composition for predicting clinical benefit in response to CTLA4 therapy comprising miR-211 and a melanoma-associated gene selected from the group consisting of CD5L, IL12RB2, FAIM3, PTCRA, CD2, CD6, CXCL13, CD3D, CD3E, CD3G, LCK, T cell receptor alpha gene, T cell receptor beta gene, GNLY, GZMA, GZMB, GZMH, GZMK, PRF1, CD19, CD72, FCRL1/3, MS4A1, CTLA4, LAG3, FCRL1, FCRL3, SIGLEC8, and FAIM3/TOSO synthesized cDNA, or a kit, comprising reagents for assaying a biological sample from a subject with cancer for: (a) aberrant expression of at least one resistant cancer-associated gene or miRNA, or (b) aberrant expression of at least one beneficial cancer-associated gene or miRNA. 54.-58. (canceled)
 59. A method of treating cancer in a subject in need thereof, comprising: administering a therapeutically effective amount of one or more CTLA4 inhibitor agents to the subject, wherein the subject is identified as (a) not having aberrant expression of at least one resistant cancer-associated gene or miRNA, or (b) having aberrant expression of at least one beneficial cancer-associated gene or miRNA; or a method of treating cancer in a subject in need thereof, comprising: (a) analyzing a biological sample from the subject for: (i) aberrant expression of at least one resistant cancer-associated gene or miRNA, wherein the aberrant expression of the at least one resistant cancer-associated gene or miRNA is not present in the biological sample, or (ii) aberrant expression of at least one beneficial cancer-associated gene or miRNA, wherein the aberrant expression of the at least one beneficial cancer-associated gene or miRNA is present in the biological sample; (b) identifying the subject as a candidate for receiving one or more CTLA4 inhibitor agents; and (c) administering a therapeutically effective amount of the one or more CTLA4 inhibitor agents to the subject; a method of treating cancer comprising administering an effective amount of a CTLA4 inhibitor and an effective amount of a HMGB1 receptor agonist; or a method of treating cancer comprising administering an effective amount of a CTLA4 inhibitor and an effective amount of a Xg28-CGA antagonist; or a method of treating cancer comprising administering an effective amount of a CTLA4 inhibitor and an effective amount of an agonist or inducer of autophagy; or a method of treating cancer comprising administering an effective amount of a CTLA4 inhibitor and an effective amount of a agonist or inducer of miR-211, miR-185 and/or miR-513A2; or a method of identifying a subject with cancer as a candidate for receiving one or more CTLA4 inhibitor agents, comprising: (a) analyzing a biological sample from the subject for: (i) aberrant expression of at least one resistant cancer-associated gene or miRNA, wherein the aberrant expression of the at least one resistant cancer-associated gene or miRNA is not present in the biological sample, or (ii) aberrant expression of at least one beneficial cancer-associated gene or miRNA, wherein the aberrant expression of the at least one beneficial cancer-associated gene or miRNA is present in the biological sample; and (b) identifying the subject as a candidate for receiving one or more ctla4 inhibitor agents. 60.-69. (canceled)
 70. A method of determining whether administration of a CTLA4 inhibitor and a HMGB1 receptor agonist to a subject with melanoma will result in clinical benefit in the subject comprising: obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether administration of a CTLA4 inhibitor and a HMGB1 receptor agonist will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample; or a method of determining whether administration of a CTLA4 inhibitor and a Xq28-CGA antagonist to a subject with melanoma will result in clinical benefit in the subject comprising: obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether administration of a CTLA4 inhibitor and Xg28-CGA antagonist will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample; or a method of determining whether administration of a CTLA4 inhibitor and an autophagy agonist to a subject with melanoma will result in clinical benefit in the subject comprising: obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether administration of a CTLA4 inhibitor and an autophagy agonist will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample; a method of determining whether administration of a CTLA4 inhibitor and a miR-211, miR-185 and/or miR-513A2 agonist to a subject with melanoma will result in clinical benefit in the subject comprising: obtaining a test sample from a subject having or at risk of developing melanoma; determining the expression level of at least one melanoma-associated gene in the test sample; comparing the expression level of the melanoma-associated gene in the test sample with the expression level of the melanoma-associated gene in a reference sample; and determining whether administration of a CTLA4 inhibitor and an miR-211, miR-185 and/or miR-513A2 agonist will inhibit melanoma in the subject if the expression level of the melanoma-associated gene in the test sample is differentially expressed as compared to the level of the melanoma-associated gene in the reference sample. 71.-92. (canceled) 